The Biology of the Breast Cell
The CBCRP encourages new research to understand the pre-cancerous events in the breast that lead to cancer at the tissue, cell, molecular, and gene level. The Program also funds all aspects of basic research on tumors as they progress from DCIS to invasive breast cancer. These studies represent the groundwork for envisioning new biomarkers for disease prognosis, therapies, and detection strategies.
Research Conclusions
Steroid Receptor Coactivators in Mammary Gland Development.
Cells in normal breast tissue and in estrogen receptor (ER)-positive breast cancers need estrogen to grow. Breast cells that do not get estrogen stop proliferating and die. This is why ER-positive breast cancers are treated with drugs that block estrogen activity. Shi Huang, Ph.D., at The Burnham Institute, La Jolla, and colleagues discovered and then investigated a new tumor suppressor gene, RIZ1, and the protein it produces. The RIZ1 gene and its protein are frequently missing in human cancers, particularly in breast cancers. The team found laboratory evidence that suggests that the breast needs RIZ1 to respond to the hormones estrogen and progesterone. They also found that the RIZ1 enzyme appears to affect other proteins in the cell’s nucleus. As a result, some genes may be more likely to respond to the commands of the estrogen receptor. For example, they found that reducing RIZ1 levels decreased production of a breast cancer-associated gene called pS2. This new understanding of estrogen receptor function may lead to the development of new ways to prevent and treat breast cancer.
Genetic Aspects of Physiological Response During Lactation.
When a clump of tumor cells grows too large, the level of oxygen in the tissue decreases (i.e., hypoxia). In response, a protein, HIF-1, increases and activates genes that control new blood vessel growth. Recent studies have shown that high levels of HIF-1 are present in a variety of tumors, including breast tumors. Randall S. Johnson, Ph.D., at the University of California, San Diego, investigated whether the HIF-1 response to lowered oxygen levels contributes to mammary gland development and the production of milk in mice. They found that mice that lack HIF-1 function do not develop sufficient numbers of alveoli, the small glands that produce milk, and fail to properly nourish their young. They also found that when mice lack a protein called von Hippel-Lindau (VHL), HIF-1 is overproduced. This, in turn, increases vascular endothelial growth factor (VEGF), which regulates the new blood vessels tumors need to grow. These findings could lead to new ways to block blood vessel growth in breast tumors and to new breast cancer treatments. Results from this research were published in Development 130:1713-24 (2003).
Effect of Breast Cell Environment on Repair of DNA Damage.
Breast cancer occurs mostly in the epithelial cells—the cells that line the breast duct. These cells are in contact with a basement membrane, a thin layer of connective tissue.
Aylin Rizki, Ph.D., at the Lawrence Berkeley National Laboratory, investigated how communication between cells and the basement membrane affects a cell’s ability to repair damage to its DNA. When the DNA is not repaired properly it can accumulate genetic changes, which sets the stage for cancer to occur. Dr. Rizki and her colleagues focused on a mechanism called the double-strand break repair pathway that prevents mutations. Double strand breaks can be caused by the radiation therapy used to treat breast cancer. Dr. Rizki’s findings suggest that basement membrane signaling is important in regulating double-strand break repair and in controlling how DNA responds to radiation. Her team is continuing to explore the effects of this signaling on DNA. They are also looking for the molecules that relay the signals from the basement membrane to the repair mechanism. Results from this research were published in Nature 411:713-16 (2001), Differentiation 70:537-46 (2002), and Signal Processing 5:147-53 (2003) and 83:729-743 (2003).
The Importance of Growth Inhibitory Signals in Normal Breast Cells.
HER-2 is a protein found in larger than normal amounts in about 30% of breast cancer cases. Scientists do not yet fully understand how having too much HER-2 promotes breast cancer. Cindy Wilson, Ph.D., at the University of California, Los Angeles, is testing the hypothesis that HER-2 promotes breast cancer by inhibiting the action of proteins in the breast that are the body’s first line of defense against the disease. Dr. Wilson and her colleagues studied both normal breast cells and breast cancer cells. They found that higher than normal levels of HER-2 can make some cells less sensitive to a protein called transforming growth factor beta (TGF-ß), which may control the growth of breast epithelial cells. They also found that higher than normal levels of HER-2 can make aggressive breast cancer cells more sensitive to TGF-ß. This research could lead to the development of new treatments for women with HER2-positive breast cancer that combine the anti-HER2 drug Herceptin with drugs that stimulate TGF-ß.
Identification of BRCA1 Ubiquitylation Targets.
Women who have inherited a mutation in a gene called BRCA1 are at higher risk for developing breast and ovarian cancer. How the normal version of BRCA1 functions at the molecular level to suppress tumor development is still not known. Peter Kaiser, Ph.D., of the University of California, Irvine, explored the genetic regulation of the BRCA1 gene through a process of protein degradation, called ubiquitylation. Dr. Kaiser compared differences in protein degradation between cells with a BRCA1 gene that worked properly and cells with a BRCA1 gene that did not. He and his colleagues went on to develop a novel approach, called SILAC (stable isotope labeling by amino acids in cell culture), which will allow them to complete their protein analysis. Dr. Kaiser received a second grant from the CBCRP in 2005 to continue this project. This research has the potential to advance our understanding of how the BRCA1 gene keeps tumors from developing, which could lead to new ways to treat women with BRCA1 gene mutations.
Understanding Telomere Dynamics in the Breast.
Telomeres, which cap the ends of chromosomes, shorten as we age, and when they get too short, a cell can no longer divide. Telomeres are made by a special enzyme called
telomerase. Cancer cells learn how to reactivate telomerase. This keeps the telomeres from getting too short, allowing the cell to divide indefinitely. Steven Artandi, Ph.D., at Stanford University, used mice to study how normal breast cells respond to telomere shortening as they age and how breast cancer develops. Dr. Artandi and his team found that when the telomerase enzyme is turned off, the mice have short telomeres, which affects how stem cells in the breast function. Dr. Artandi received CBCRP funding in 2005 to further investigate the role of telomerase in stem cell function. This research on how breast cancer evolves could lead to new methods of prevention and treatment.
Analysis of Genes Predictive of Breast Cancer Metastasis.
Women who have cancer that has metastasized (spread to other parts of the body) have a poor prognosis. Jeffrey Gregg, M.D., from the University of California, Davis, and colleagues examined the action of an enzyme called phosphoinositol kinase 3 (PI-3 kinase) in two lines of mouse mammary tumor cells (mammary tumors in mice are the equivalent of breast tumors in humans). The goal was to learn more about metastasis. They found that when PI-3 kinase is turned on, the tumors were more likely to spread to the lung than to other parts of the body. They also found that tumors that metastasize quickly were more likely to have more copies of the gene osteopontin (OPN) and more of its proteins than tumors that were less likely to spread. These findings led Dr. Gregg and his colleagues to conclude that there is a link between cancers that metastasize, PI-3 kinase, and OPN. His group is continuing to study the relationship between PI-3 kinase and genes like OPN. This research could lead to new way of determining which breast tumors are most likely to spread to other parts of the body.
The Role of Matrix Metalloproteinase 13 in Breast Cancer.
The normal breast contains many cell types, including milk-producing (epithelial) cells and stromal (supporting) cells. Most research on breast cancer focuses on the genetic changes in the epithelial cells, which is where breast cancer begins. However, the stromal cells also undergo changes as breast cancer evolves. Mikala Egeblad, Ph.D., at the University of California, San Francisco, studied an enzyme called matrix metalloproteinase 13 (MMP-13) that is secreted by the supporting stromal cells and that appears to play a role in breast cancer. Dr. Egeblad and her colleagues found that there was an overabundance of MMP-13 in breast tumors in several different mouse models of breast cancer. They also studied the relationship between MMP-13 and a molecule, called type I collagen, that activate MMP-13 and has been linked to the initiation and spread of breast cancer. Their findings suggest that interactions between type I collagen and MMP is necessary for normal breast development. They also found that MMP-14, not MMP-13, was the enzyme that played a role in this process. Dr. Egeblad intends to continue to study type I collagen and the MMP enzymes to determine if the molecule could be used to help doctors assess whether breast cancer is present or is likely to spread. Results from this research were published in Molecular and Cellular Biology 23:8614-25 (2003).
A Novel Predictive Test for HER-2/EGFR Ab-based Therapeutics.
About 30 percent of breast tumors have larger than normal amounts of a protein called HER-2. This protein, which plays a crucial role in cell differentiation, can make cancers more aggressive. Trastuzumab (brand name Herceptin) is used to treat breast cancers that make too much HER-2
protein. It is believed that trastuzumab works by attaching itself to the HER-2 proteins on the surface of the tumor cells and then pushing these proteins back into the cell, which keeps the tumor from growing. This process is called internalization. Verena Kallab, M.D., at the University of California, San Francisco, developed a new technique using circulating tumor cells (CTCs) in mouse models of human breast cancer to quickly evaluate whether and to what extent a cancer treatment (trastuzumab) that targets the HER-2 protein is promoting internalization of the receptor. The new technique could help assess the potential effectiveness of new cancer treatments that target breast tumors that overproduce the HER-2 protein.
Hox Transcriptional Regulation of Breast Tumor Angiogenesis.
For a tumor to be able to grow and spread throughout the body it must make its own blood vessels, a process called angiogenesis. Abnormal expression of many HOX genes indicates an involvement of these transcriptional (gene) regulators in cancer progression and metastasis. Lucy East, Ph.D., at the University of California, San Francisco, and colleagues studied a protein called homeobox transcription factor D10 (HoxD10). Previous studies had found that Hox factors control how the endothelial cells—the cells support and feed breast cancer cells—move and grow. Using mice, Dr. East found that HoxD10 did not appear to affect an enzyme that is needed for cancer cells to grow and spread (metastasize). Dr. East is continuing to explore how HoxD10 is able to keep angiogenesis from occurring by acting on a major signaling protein, called Akt. Learning how HoxD10 functions could lead to the development of new breast cancer treatments that can stop cancer cells from metastasizing.
Cell-Killing Effect of Orphan Receptor TR3 in Breast Cancer.
Vitamin A compounds, called retinoids, are being studied for their ability to prevent or treat cancer. Research has shown that one of these compounds, called AHPN, can cause breast cancer cells to die, and that a protein called TR3 (a critical modulator of cancer cell death by its ability to migrate from the nucleus to mitochondria) plays an important role in this process. Nathalie Bruey-Sedano, Ph.D., at The Burnham Institute, La Jolla, found that combining vitamin A compounds with chemotherapy drugs used to treat breast cancer made the chemotherapy drugs more effective at killing breast cancer cells. Dr. Bruey-Sedano and her colleagues found this occurred in both hormone-sensitive and hormone-independent breast cancer cells. The team also was able to identify several genes related to cell death that were altered when the combination therapy was used. These findings could lead to a new approach for treating breast cancer.
Role of Pak Kinase in Breast Cancer Cell Cycle Progression.
Pak kinase is a type of protein that is believed to play a role in how cells transform from normal to cancerous. Beatriz Maroto, Ph.D., at the Scripps Research Institute, La Jolla, studied the role of Pak kinase in breast cancer cells during cell division, a process called mitosis. Dr. Maroto and her colleagues found that Pak activity is required for cells to grow and divide. They also identified a previously unknown way in which Pak operates through a second family of protein kinases (Polo-like kinases) at the time the nucleus divides into two new cells. This research could lead to the development of new breast cancer treatments that keep breast cancer cells from growing and dividing by inhibiting Pak kinase.
Regulation of Estrogen Response by Corepressors.
Breast development is regulated by interactions between hormones and proteins called growth factors. The hormone estrogen is one of the most important in this process. It binds to the estrogen receptor, which is regulated by proteins called corepressors. Martin Privalsky, Ph.D., at the University of California, Davis, investigated chemical interactions between corepressors and other proteins called kinases, and how this affects the estrogen receptor. Dr. Privalsky found that messages sent by growth factors such as epidermal growth factor are able to activate some corepressors 9SMRT), but do not activate other closely related corepressors (N-CoR). This research could lead to the development of new therapies for women whose breast tumors acquire resistance to anti-estrogen chemotherapy.
The Functions of BRCA2 in Repairing DNA Damage.
Women with an abnormal version of the BRCA2 gene are more likely to get breast cancer. The protein produced by the normal BRCA2 gene interacts chemically with a protein complex in cells, Rad51. Rad51 is involved in a part of the process of DNA repair called homologous recombination repair. Yi-Ching Lio, Ph.D., at the Lawrence Berkeley National Laboratory, used molecular biology methods to investigate the normal BRCA2 protein. Dr. Lio found cellular and biochemical evidence that the interaction between BRCA2 and Rad51 is necessary for homologous recombination repair. Dr. Lio and his colleagues also performed studies on the Rad51 family of proteins. Their research produced the first in vivo evidence of how Rad51C works in homologous recombination repair. This research could shed light on why a mutated BRCA2 gene leads to a high number of mutations in tumor genes, and also help scientists understand why cancer cells can repair their DNA, even after being treated with DNA-damaging chemotherapy. Results from this research were published in the Journal of Biological Chemistry 279: 42313-20 (2004).
The Detailed Structure of a Model Breast Cancer Genome.
The chromosomes and the genes they carry that are found inside breast cancer cells often look very different from the chromosomes found in normal breast cells. Colin Collins, Ph.D., at the University of California, San Francisco, used a new technique called End Sequence Profiling to identify all the genetic differences between breast cancer cells and normal cells. End Sequence Profiling uses some of the same methods that were used to map the human genome. Dr. Collins began by creating a bacterial artificial chromosome (BAC) library for the tumor being studied. He then compared the BAC with a reference library of chromosomes, which allowed him to quickly see if there were extra genes or missing ones. To date, Dr. Collins and his team have demonstrated the ability of End Sequence Profiling to identify genetic differences in tumors in the brain, breast, ovary, and prostate. This approach could help lead to the development of new breast cancer treatments. Results were published in the Proceedings of the National Academy of Sciences USA 100:7696-7701 (2003) and Bioinformatics 1:1-12 (2003).
Molecular Analysis of BRCA1 Function.
Women who have inherited a mutation in a gene called BRCA1 are at higher risk for developing breast and ovarian cancer. BRCA1 is hard to study in animal models because mice that lack the BRCA1 gene do not live very long. Quan Zhu, Ph.D., at the Salk Institute for Biological Studies, La Jolla, attempted to develop a mouse that would be a better model for breast cancer using a new gene expression vector. Although Dr. Zhu made progress toward this goal, his efforts did not result in the creation of any mice that carried a human BRCA1 gene.
Locating Novel Breast Cancer Genes Using DNA Microarrays.
Breast cancer occurs when genes that control normal cells go awry. Tumor suppressor genes, which put the brakes on cell growth, are frequently missing in breast cancer. Jonathon Pollack, M.D., Ph.D., at Stanford University School of Medicine, used DNA microarrays (gene-chips) that can look simultaneously at more than 26,000 genes from human tumor samples. The goal was to identify novel tumor suppressor genes in breast cancer by focusing on sites where DNA was missing. Dr. Pollack and his team were able to characterize DNA deletions in 50 different breast cancer cell lines and 144 primary breast tumors. Now they will focus their research efforts on the tumor suppressor genes where DNA is missing. This research could lead to new genetic tools that will help oncologists assess how aggressive a cancer is and to the development of new treatment options.
Genes That Modulate Dioxin-Induced Breast Cancer.
Dioxins are widespread environmental toxins known to cause cancer. Several studies suggest dioxin may be responsible for some breast cancer cases. Quan Lu, Ph.D., of Stanford University, searched for genes that make breast cells more likely to become cancerous if exposed to dioxin. The research team used two techniques. The first, RHKO, has been used to discover genes that inhibit tumor growth. The second, microarrays, is a technology that allows a researcher to study thousands of genes simultaneously. These techniques allowed Dr. Lu to identify several previously unknown genes that are involved in breast cancers caused by dioxins. This work could lead to new ways to prevent, diagnose and treat cancers caused by dioxins and to identify individuals who are most likely to develop dioxin-induced cancers. Results from this research were published by Dr. Lu and his mentor Dr. Stanley Cohen in the Proceedings of the National Academy Sciences USA 100:7626-31 (2003).
Tumor Suppression by Dystroglan in Breast Epithelial Cells.
Normal breast epithelial cells (the cells where most cancers arise) are organized in a single layer, with one side of each cell attached to another type of cell, collectively called the basement membrane. Proteins attach the cells together. The cell-basement membrane interaction helps prevent uncontrolled cell growth. There is considerable evidence that restoring critical attachment functions in the very early stages of breast cancer will reverse the disease. John L. Muschler, Ph.D., of the Lawrence Berkeley National Laboratory, studied a basement membrane protein, called laminin, which interacts with a protein present on the surface of breast cells called dystroglycan (DG). In addition to interacting with laminin, DG tells the cell to stop growing. DG appears to be absent or
nonfunctional in breast cancer. Dr. Muschler created breast epithelial cells in which the DG gene can be selectively deleted using a technology called “cre-lox recombination.” This allowed him to compare how cells with and without DG function and to learn more about what DG does. Dr. Muschler also explored what causes DG to stop functioning in breast cancer cells. He found that the sugar molecules that are on DG and are necessary for it to function have been altered on invasive cancer cells. This research could lead to the development of new breast cancer treatments that work by restoring DG functioning.
Role of PTEN/Akt Pathway in Progression of Ductal Carcinoma in Situ.
Ductal carcinoma in situ (DCIS) is considered a pre-cancer and not true cancer because the altered cells are confined to the breast duct. It is known that about 25–30 percent of DCIS lesions will eventually progress to become invasive cancer, but it is not known how to predict which cases have the potential to become invasive. Shikha Bose, M.D., at Cedars-Sinai Medical Center in Los Angeles, explored how DCIS progresses to invasive breast cancer by studying PTEN, a recently-identified tumor suppressor gene that is missing in invasive breast cancer. Dr. Bose and her team compared genetic changes in tissue from women with DCIS to that of women who had invasive breast cancer. They were able to identify certain pathways (series of chemical reactions within cells) activated early in breast cancer. They also found proteins that were present at higher levels in invasive cancers. This research could lead to the development of genetic markers that physicians could use to identify which cases of DCIS are most likely to become invasive. These genetic markers might also provide insight into which proteins and genes could be investigated for new drug development.
Infinite Expansion of Breast Tumor Samples in Culture.
Research on breast cancer cells growing in lab cultures is limited to about eight types of cells. These cells came decades ago from aggressive tumors that had spread to other parts of the body. This makes it hard to investigate genes and proteins present at earlier stages of the disease. Drugs tested against the currently available cells may not work the same way against tumors caught in early stages of breast cancer. Previous attempts to grow more kinds of breast cancer cells in lab cultures have failed. Shanaz Dairkee, Ph.D., at the California Pacific Medical Center Research Institute, San Francisco, developed a new method that would allow scientists to grow cells in lab cultures from the majority of breast cancer cases. Dr. Dairkee and colleagues showed that this new method produced permanent breast cancer cell lines directly from a variety of human tumors and that these cancer cells retained the same genetic profile as the original tumor, differed from existing tumor lines, and were capable of forming tumors in mice. Dr. Dairkee has received additional funding from the National Institutes of Health to pursue the goal of making these new cells lines available to other investigators. Research using these cells lines could lead to the discovery of new molecules involved at all stages of the disease, and possibly drugs to target these molecules. It could also lead to individualized therapy, where drugs could be tested against a woman’s tumor cells before treatment. Results from this research were published in BMC Genomics 5:47-56 (2004).
Does the BLM Gene Co-Regulate BRCA1 in DNA Damage Response?
The normal form of the BRCA1 gene prevents uncontrolled cell growth. Women who inherit a mutation in this gene are more likely to get breast cancer. Albert Davalos, Ph.D., at Lawrence Berkeley National Laboratory, investigated whether another gene called BLM and the protein it produces interacts with the normal BRCA1 gene to prevent uncontrolled cell growth. Dr. Davalos and his colleagues found that the tumor suppressor protein p53 works with the BLM protein to protect breast epithelial cells when they grow and divide. They also found that two signaling proteins, ATM and ATR, are necessary for BLM to operate properly. Next, they will study breast epithelial cells in a 3-D cell culture system that is similar to normal tissue. This research has the potential to uncover biological markers that could provide a new method for detecting breast cancer early before it has spread. Findings from this research were published in the Journal of Biological Chemistry 162:1197-1209 (2003); Cell Cycle 3:1579-86 (2004); and Experimental Cell Research 298:17-27 (2004). Dr. Davalos received additional funding from the CBCRP through an IDEA grant to continue this line of research.
Molecular Pathogenesis of Metastatic Breast Cancer.
Despite all currently available treatments, the majority of women who develop advanced, metastatic breast cancer will eventually die. Robert Debs, M.D., at California Pacific Medical Center Research Institute, San Francisco, used a new technology called cDNA microarray analysis to search for combinations of genes that all work together to allow breast cancer cells to spread to other body parts, a process known as metastasis. They found that FKBPr38, a gene with no previously identified function, helped breast cancers to metastasize. They also identified a network of related genes—FKBP12, MMP-9, and syndecan-1—that together play an important role in causing breast cancers to spread. Knowing which genes play a role in metastases will allow researchers to better understand what causes breast cancer to spread to other areas of the body and could lead to new breast cancer treatments that target these genes. Findings from this research were published in the Proceedings of the National Academy of Sciences USA 100:13543-38 (2003) and 100:14253-58 (2003); and Molecular Therapy 10:706-718 (2004).
Identification and Prognostic Value of ERß in Breast Cancer.
Estrogens promote breast cancer by binding to the estrogen receptor (ER) molecules in breast epithelial cells. Hormone treatments, such as tamoxifen and a class of drugs called aromatase inhibitors, treat breast cancer by blocking estrogen. However, many tumors eventually become resistant to these drugs. There are two distinct estrogen receptors, ER alpha and ER beta (ERß). ER alpha is currently used to classify tumors as hormone sensitive. The significance of ERß is not known. Dale Leitman, M.D., Ph.D., at the University of California, San Francisco, attempted to develop an accurate test to measure the level of ERß in tumors and to assess whether the presence of ERß makes tumors more aggressive. Dr. Leitman found that ERß was present in about one-third of the tumors he evaluated. However, ERß did not appear to be related to the likelihood that a tumor was more or less likely to spread to other parts of the body. These findings have advanced our understanding of ERß and lay the groundwork for future research on the estrogen receptor molecules.
Three-Dimensional Modeling of Breast Cancer Progression.
Breast cells must respond to many different types of external chemical signals transmitted through hormones and proteins called growth factors. It is possible that cells in certain locations in the breast and at certain stages in their abnormal development may be most likely to become cancerous. Carlos Ortiz de Solorzano, Ph.D., at the Lawrence Berkeley National Laboratory, used mice that have been genetically engineered to develop tumors that mimic a deadly type of breast cancer, erbB2-positive. The goal was to study where in the mouse mammary gland (the mouse equivalent of the breast) the tumors arise, and to plot the cell-by-cell presence of key proteins. To date, the research team has partially constructed 21 mammary glands, 10 from normal mice and 11 from genetically engineered mice, at six-week intervals. When their work is complete, they will have produced a progressive “atlas” to visualize the development of breast cancer. This model of cancer progression could lead to new treatments that target or repair the molecular mechanisms that play a role in the initiation and growth of breast cancer. Findings from this research were published in the Journal of Biomedical Optics 9:444-53 (2004).
Mechanism of Estrogen Receptor Loss in Breast Cancer.
Between 30 and 50 percent of human breast cancers have a mutant tumor suppressor gene, p53. Using mice, Keon Wook Kang, Ph.D., at the University of California, Irvine, examined the role of the p53 gene on estrogen signaling in the growth of mammary epithelial cells—the cells where breast cancer begins. Dr. Kang and his mentor, Dr. Eva Lee, found that mammary epithelial cells with a mutant p53 gene responded differently to estrogen than did cells with normal p53 genes. These findings support the notion that p53 affects the role estrogen has on mammary epithelial cells and could lead to new ways to treat breast cancer.
Molecular Analysis of DCIS Progression in a Mouse Model.
Breast cancer development is a multi-step process. DCIS (ductal carcinoma in situ) is a type of pre-malignant breast cancer that can transform into invasive cancer. To learn more about this progression, better mouse models for DCIS are needed. Ruria Namba, Ph.D., at the University of California, Davis, developed a mouse cell line in which mammary cancer (the mouse equivalent of the breast cancer) progresses from DCIS to invasive cancer. Dr. Namba’s research confirmed that the model reflects the biology of DCIS that occurs in humans and that the cell line can be transplanted into other mice. This mouse model could be used to develop new ways to prevent and treat breast cancer. Findings from this research were published in Clinical & Experimental Metastasis 22:47-58 (2005); Molecular Cancer Research 2:453-463 (2004); and Breast Cancer Research 5:S7 (2003).
Grants in Progress: 2005
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Role of Bl-1 Protein in Breast Cancer Apoptosis
Beatrice Bailly-Maitre
The Burnham Institute
Role of FGF10 in Early Mouse Mammary Gland Development
Saverio Bellusci
Childrens Hospital Los Angeles
Prognostic Value of Ras Activation in Breast Cancer
Gerry Boss and Anne Wallace
University of California, San Diego
Epithelial Polarity, Organization and the Angiogenic Switch
Nancy Boudreau
University of California, San Francisco
Proteomic Profiling of Adhesive Structures in Breast Cancer
Jason Bush
The Burnham Institute
Characterizing Breast Cancer Cells in Blood and Bone Marrow
Robert Carlson
Stanford University
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Role of Chromatin Regulator in Breast Cell Growth
Hongwu Chen
University of California, San Francisco
Alternative pre-mRNA Splicing in Mammary Epithelial Cells
John Conboy
Lawrence Berkeley National Laboratory
Profiling Enzyme Activities in Human Breast Cancer
Benjamin Cravatt and Stephanie Jeffrey
The Scripps Research Institute and Stanford University
Stem Cells in Breast Cancer Metastasis
Brunhilde Felding-Habermann, John Yates and Evan Snyder
Scripps Research Institute and The Burnham Institute
Oxidative Stress and Estrogen Receptor Structural Changes
Bradford Gibson and Christopher Benz
Buck Institute for Age Research
Role of Oxidative DNA Damage to Breast Tumor Progression
Paul Henderson
Lawrence Livermore National Laboratory
Axon Guidance Proteins in Mammary Gland Development
Lindsay Hinck
University of California, Santa Cruz
Protective Role of Estrogen Receptor Beta in Mammary Gland
Leslie Hodges
University of California, San Francisco
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Translational Proteomics of Normal to Benign Breast Disease
Dave Hoon, Armando Giuliano and Lori Wilson
John Wayne Cancer Institute
Study of the Apoptotic Phenotype as a Hallmark of Malignancy
Nola Hylton
University of California, San Francisco
Role of IKKα in Mammary Gland Development
Michael Karin
University of California, San Diego
Dissection of Signaling Events in the Mammary Gland in Vivo
Yuehai Ke
The Burnham Institute
In Vivo Gene Expression Profiling of Developing Mammary Gland
Hosein Kouros-Mehr
University of California, San Francisco
Understanding Aging Effects in the Breast
Ana Krtolica
Lawrence Berkeley National Laboratory
Identifying Metastatic Breast Cells from Peripheral Blood
Kristin Kulp
Lawrence Livermore National Laboratory
Targeting of DNA Methylation in Mammary Epithelial Cells
David Liston
Salk Institute
Cloning of Putative Tumor Suppressor Gene on the X Chromosome
Sergei Malkhosayan
The Burnham Institute
Does Disregulaton of Centrosomes Cause Breast Cancer?
Kimberly M. McDermott
University of California, San Francisco
Statistical Techniques for Breast Biology and Cancer Research
Saira Mian
Lawrence Berkeley National Laboratory
Discovering Novel Cell-ECM Interactions in Breast Cells
John Muschler
California Pacific Medical Center Research Institute
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Targeting Estrogen Receptors to Mammary Epithelial Cells
Richard H. Price, Jr.
University of California, San Francisco
Novel Genes in Mammary Gland Development and Cancer
Euan Slorach
University of California, San Francisco
The Breast Cancer Suppressor Maspin: A Proteasome Inhibitor?
Jeffrey Smith
The Burnham Institute
A Novel Approach to Inactivate the Estrogen Receptor
Alex So
University of California, San Francisco
Angiogenesis in Hyperplasia to In-Situ Breast Cancers
Min-Ying (Lydia) Su
University of California, Irvine
Early Transitions in Breast Cancer
Thea Tisty
University of California, San Francisco
The Role of Gli3 in Mouse Embryonic Mammary Gland Formation
Jacqueline Veltmaat
Children’s Hospital, Los Angeles
Normal Mammary Biology of Phosphorylated Prolactin
Ameae Walker
University of California, Riverside
Functional Analysis of BORIS, A Novel DNA-binding Protein
Paul Yaswen
Lawrence Berkeley National Laboratory
Research Initiated in 2005
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Breast Cancer Studies in a 3-D Cell Culture System
Robert T. Abraham, Ph.D.
The Burnham Institute
Reactivation of the Inactive X Chromosome and Breast Cancer
Angela Andersen, Ph.D.
University of California, San Francisco
Role of Telomerase in Mammary Stem Cell Function
Steven Artandi, Ph.D.
Stanford University
Defining Mammary Cancer Origins in a Mouse Model of DCIS
Alexander Borowsky, M.D.
University of California, Davis
Integrated Proteomic and Metabolic Analysis of Breast Cancer
Kyle P. Chiang
The Scripps Research Institute
The Role of the ECM in Breast Cancer DNA Damage Repair
Albert R. Davalos, Ph.D.
Lawrence Berkeley National Laboratory
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Novel Approach to Analyze Estrogen Action in Breast Cancer
Brian P. Eliceiri, Ph.D.
La Jolla Institute for Molecular Medicine
Regulation of Mammary Epithelial Invasion by MMPs and FGFs
Andrew J. Ewald, Ph.D.
University of California, San Francisco
Survivin: Target for Breast Cancer Brain Metastases
Florence M. Hofman, Ph.D.
University of Southern California
Stem Cells of Molecularly Diverse ER Negative Breast Cancers
Stephanie Jeffrey, M.D.
Stanford University
Identification of BRCA1 Ubiquitylation Targets
Peter Kaiser, Ph.D.
University of California, Irvine
Apaf-1 is a Transcriptional Target for the ZNF217 Oncogene
Sheryl R. Krig, Ph.D.
University of California, Davis
Identifying Metastatic Breast Cells from Peripheral Blood
Kristen S. Kulp, Ph.D.
Lawrence Livermore National Laboratory
The Role of B-Myb in Human Breast Cancer Progression
Joseph Lipsick, M.D.,Ph.D.
Stanford University
Defining Mutagenesis Pathways in Breast Cancer Evolution
Ewa Lis
Scripps Research Institute
Evaluating the Role of RIN1 in Breast Cancer
Marc Milstein
University of California, Los Angeles
A Novel Epithelial-Stromal Model of Metastatic Breast Cancer
Richard M. Neve, Ph.D.
Lawrence Berkeley National Laboratory
Histone Methylation as a Marker of Breast Cancer Progression
Judd C. Rice, Ph.D.
University of Southern California
Structural Analysis of Cancer-Relevant BCRA2 Mutations
Henning Stahlberg, Ph.D.
University of California, Davis
Imaging RhoC-induced Breast Cancer Invasion and Angiogenesis
Konstantin V. Stoletov, Ph.D.
The Scripps Research Institute
Role of Integrins in Lymphangiogenesis During Breast Cancer
Barbara Susini, Ph.D.
University of California, San Diego
A Role for p53 and Splicing Factor SAP145 in Breast Cancer
Lan N. Truong
University of California, Irvine
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Modulation of TGF-beta Signaling in Mammary Epithelial Cells
Xiaoman Xu
University of California, Irvine
The Role of LMO4 in Breast Cancer
Zhengquan Yu, Ph.D.
University of California, Irvine
