MECHANISMS OF BREAST DEVELOPMENT AND CARCINOGENESIS

Summary

Principal Investigator: Robert A Weinberg
Abstract: DESCRIPTION (provided by applicant): This application presents a proposal to extend for a third five-year funding period a Program Project Grant that has supported a network of interacting research groups in the Boston-Cambridge area whose research is focused on the genetic, molecular, and cellular mechanisms leading to the formation of human breast cancers. The findings of this research are increasingly being applied and related to the problems of clinical breast cancer development, diagnosis, and treatment. As described below in this proposal, this Program has fostered fruitful interactions between the participating research groups in the past and promises to do so in the future. Much of the synergy that has arisen in the past among these groups and is proposed for the future funding period has derived from the fact that the participating groups have complementary interests, thereby attacking the breast cancer problem using a number of distinct experimental approaches. Included among these complementary strategies are studies of (I) how defects in the BRCA1&2 proteins lead to compromised DNA repair and resulting basaloid carcinomas of the breast;(ii) how D-type cyclins drive the proliferation of mammary epithelial cells in as many as half of human breast cancers;(iii) how various regulators of mammary epithelial cell biology affect the apoptosis of these cells and their behavior early in breast cancer development;(iv) how estrogen and progesterone receptors affect the biology of mammary epithelial cells;(v) how breast cancer cells acquire the ability to metastasize and succeed in founding macroscopic metastases at distant tissue sites;(vi) how changes of gene expression patterns provide indications of the nature of the initial steps of human breast cancer development. The complementarities of these approaches have led to many examples of collaboration and cross-fertilization over the past decade that will continue in the proposed future funding period. In spite of extensive research over the past three decades, we still possess, at best, only a fragmentary understanding of how the different types of human breast cancers begin. The mechanisms that lead to the formation of these tumors must be elucidated at the level of molecules, cells, and ultimately tissues. The proposed research is focused on understanding the molecular and cellular mechanisms leading to breast cancer development, because it is clear that novel, truly effective prognostic tools and therapies can only be developed in the future if these disease-causing mechanisms are uncovered. Accordingly, a number of the research directions described herein have the potential, if successful, to suggest approaches for developing novel, improved diagnostic arid therapeutic strategies that can be used in the breast cancer clinic of the future.
Funding Period: 1999-03-18 - 2014-01-31
more information: NIH RePORT

Top Publications

  1. pmc JARID1B is a luminal lineage-driving oncogene in breast cancer
    Shoji Yamamoto
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA Center for Functional Cancer Epigenetics, Dana Farber Cancer Institute, Boston, MA 02215, USA Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 25:762-77. 2014
  2. pmc Proteomic identification of a direct role for cyclin d1 in DNA damage repair
    Siwanon Jirawatnotai
    Department of Cancer Biology, Dana Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA 02215, USA
    Cancer Res 72:4289-93. 2012
  3. pmc Mechanisms of BRCA1 tumor suppression
    Daniel P Silver
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cancer Discov 2:679-84. 2012
  4. pmc Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress
    Alberto Ciccia
    Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA
    Mol Cell 47:396-409. 2012
  5. pmc The outgrowth of micrometastases is enabled by the formation of filopodium-like protrusions
    Tsukasa Shibue
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Cancer Discov 2:706-21. 2012
  6. ncbi Intra-tumour heterogeneity: a looking glass for cancer?
    Andriy Marusyk
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston MA 02215, USA
    Nat Rev Cancer 12:323-34. 2012
  7. pmc Slug and Sox9 cooperatively determine the mammary stem cell state
    Wenjun Guo
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 148:1015-28. 2012
  8. pmc Outgrowth of single oncogene-expressing cells from suppressive epithelial environments
    Cheuk T Leung
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 482:410-3. 2012
  9. pmc Tumor metastasis: molecular insights and evolving paradigms
    Scott Valastyan
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 147:275-92. 2011
  10. pmc Targeting androgen receptor in estrogen receptor-negative breast cancer
    Min Ni
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02215, USA
    Cancer Cell 20:119-31. 2011

Research Grants

  1. Signaling in Inflammation, Stress, and Tumorigenesis
    GEORGE ROBERT STARK; Fiscal Year: 2013

Detail Information

Publications64

  1. pmc JARID1B is a luminal lineage-driving oncogene in breast cancer
    Shoji Yamamoto
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA Center for Functional Cancer Epigenetics, Dana Farber Cancer Institute, Boston, MA 02215, USA Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 25:762-77. 2014
    ..High luminal JARID1B activity is associated with poor outcome in patients with hormone receptor-positive breast tumors. ..
  2. pmc Proteomic identification of a direct role for cyclin d1 in DNA damage repair
    Siwanon Jirawatnotai
    Department of Cancer Biology, Dana Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA 02215, USA
    Cancer Res 72:4289-93. 2012
    ..In this review, we discuss observations linking cyclin D1 to DNA damage repair and summarize our recent findings, which show a cyclin D1 function in homologous recombination-mediated DNA repair...
  3. pmc Mechanisms of BRCA1 tumor suppression
    Daniel P Silver
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cancer Discov 2:679-84. 2012
    ..Although key mysteries remain--such as why BRCA1 tumor suppression is focused on carcinomas of the breast and ovary--the pace of discovery is increasing...
  4. pmc Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress
    Alberto Ciccia
    Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA
    Mol Cell 47:396-409. 2012
    ..We therefore propose that ZRANB3 maintains genomic stability at stalled or collapsed replication forks by facilitating fork restart and limiting inappropriate recombination that could occur during template switching events...
  5. pmc The outgrowth of micrometastases is enabled by the formation of filopodium-like protrusions
    Tsukasa Shibue
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Cancer Discov 2:706-21. 2012
    ..Hence, the formation of FLPs represents a critical rate-limiting step for the subsequent development of macroscopic metastases...
  6. ncbi Intra-tumour heterogeneity: a looking glass for cancer?
    Andriy Marusyk
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston MA 02215, USA
    Nat Rev Cancer 12:323-34. 2012
    ..We discuss the implications of intra-tumour heterogeneity in diagnostics and the development of therapeutic resistance...
  7. pmc Slug and Sox9 cooperatively determine the mammary stem cell state
    Wenjun Guo
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 148:1015-28. 2012
    ....
  8. pmc Outgrowth of single oncogene-expressing cells from suppressive epithelial environments
    Cheuk T Leung
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 482:410-3. 2012
    ....
  9. pmc Tumor metastasis: molecular insights and evolving paradigms
    Scott Valastyan
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 147:275-92. 2011
    ..Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting...
  10. pmc Targeting androgen receptor in estrogen receptor-negative breast cancer
    Min Ni
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02215, USA
    Cancer Cell 20:119-31. 2011
    ..Specific targeting of AR, Wnt or HER2 signaling impairs androgen-stimulated tumor cell growth suggesting potential therapeutic approaches for ER-/HER2+ breast cancers...
  11. pmc A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers
    Siwanon Jirawatnotai
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 474:230-4. 2011
    ....
  12. pmc Epigenetic regulation of cell type-specific expression patterns in the human mammary epithelium
    Reo Maruyama
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, United States of America
    PLoS Genet 7:e1001369. 2011
    ....
  13. pmc A non-genetic route to aneuploidy in human cancers
    Matej Krajcovic
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nat Cell Biol 13:324-30. 2011
    ..In human breast tumours, multinucleation is associated with cell-in-cell structures. These data define a previously unknown mechanism of cytokinesis failure and aneuploid cell formation that operates in human cancers...
  14. pmc Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts
    Yasushi Kojima
    Cancer Research UK Stromal Tumor Interaction Group, Paterson Institute for Cancer Research, The University of Manchester, Manchester M20 4BX, United Kingdom
    Proc Natl Acad Sci U S A 107:20009-14. 2010
    ..This autocrine-signaling mechanism may prove to be an attractive therapeutic target to block the evolution of tumor-promoting CAFs...
  15. ncbi Molecular markers for the diagnosis and management of ductal carcinoma in situ
    Kornelia Polyak
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St D740C, Boston, MA 02115, USA
    J Natl Cancer Inst Monogr 2010:210-3. 2010
    ..Comprehensive molecular studies analyzing large cohorts of DCIS with long-term clinical follow-up are necessary to resolve the many remaining questions...
  16. pmc Estrogen receptor prevents p53-dependent apoptosis in breast cancer
    Shannon T Bailey
    Center for Functional Cancer Epigenetics and Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 109:18060-5. 2012
    ..These findings suggest an improved strategy for the treatment of ER+ breast cancer using antagonists that completely block ER action together with drugs that activate p53-mediated cell death...
  17. pmc The requirement for cyclin D function in tumor maintenance
    Yoon Jong Choi
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA
    Cancer Cell 22:438-51. 2012
    ..Inhibition of cyclin D-kinase activity represents a highly-selective anticancer strategy that specifically targets cancer cells without significantly affecting normal tissues...
  18. pmc Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer
    Rinath Jeselsohn
    Authors Affiliations Center for Functional Cancer Epigenetics, Department of Medical Oncology, Dana Farber Cancer Institute Department of Medicine, Brigham and Women s Hospital Departments of Pathology and Breast Medical Oncology Program, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston Foundation Medicine, Cambridge, Massachusetts Departments of Investigational Cancer Therapeutics, Surgical Oncology, and Systems Biology and Breast Medical Oncology, The University of MD Anderson Cancer Center, Houston, Texas Fundacion de Investigacion INCLIVA Institute for Health Research Departments of Hematology Oncology, Hospital Clinico Universitario de Valencia, Valencia, Spain Jefferson Breast Care Center, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania Instituto Nacional de Enfermedades Neoplásicas INEN, Lima, Perú Breast Cancer Program, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee Teva Pharmaceuticals, Petach Tikva Oncology Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel and Section of Breast Medical Oncology, Yale School of Medicine, New Haven, Connecticut
    Clin Cancer Res 20:1757-67. 2014
    ....
  19. pmc The epigenetics of epithelial-mesenchymal plasticity in cancer
    Wai Leong Tam
    1 Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA 2 Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology MIT, Cambridge, Massachusetts, USA
    Nat Med 19:1438-49. 2013
    ....
  20. pmc Physiological modulation of endogenous BRCA1 p220 abundance suppresses DNA damage during the cell cycle
    Stoil D Dimitrov
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 27:2274-91. 2013
    ..Thus, like its loss, a surfeit of endogenous p220 function represents a threat to genome integrity. ..
  21. pmc An integrin-linked machinery of cytoskeletal regulation that enables experimental tumor initiation and metastatic colonization
    Tsukasa Shibue
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA MIT Ludwig Center for Molecular Oncology, Cambridge, MA 02139, USA
    Cancer Cell 24:481-98. 2013
    ....
  22. pmc Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells
    Wai Leong Tam
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA MIT Ludwig Center for Molecular Oncology, Cambridge, MA 02139, USA
    Cancer Cell 24:347-64. 2013
    ..Hence, identifying molecular features that shift between cell states can be exploited to target signaling components critical to CSCs. ..
  23. pmc Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics
    Sibgat Choudhury
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA
    Cell Stem Cell 13:117-30. 2013
    ..Our results suggest that pathways controlling p27(+) mammary epithelial cells and the numbers of these cells relate to breast cancer risk and can be explored for cancer risk assessment and prevention. ..
  24. pmc PDEF promotes luminal differentiation and acts as a survival factor for ER-positive breast cancer cells
    Gilles Buchwalter
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, and Center for Functional Cancer Epigenetics, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA
    Cancer Cell 23:753-67. 2013
    ..These results offer insights into the function of this ETS factor that are clinically relevant and may be of therapeutic value for patients with breast cancer treated with endocrine therapy...
  25. pmc Digital quantification of gene expression in sequential breast cancer biopsies reveals activation of an immune response
    Rinath M Jeselsohn
    Center for Functional Cancer Epigenetics, Dana Farber Cancer Institute, Boston, Massachusetts, United States of America
    PLoS ONE 8:e64225. 2013
    ....
  26. pmc Palb2 synergizes with Trp53 to suppress mammary tumor formation in a model of inherited breast cancer
    Christian Bowman-Colin
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 110:8632-7. 2013
    ..Therefore, Palb2-driven DNA damage control is, in part, distinct from that executed by Brca1 and more similar to that of Brca2. The mechanisms underlying Palb2 mammary tumor suppression functions can now be explored genetically in vivo...
  27. pmc Amplitude modulation of androgen signaling by c-MYC
    Min Ni
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA
    Genes Dev 27:734-48. 2013
    ..These results reveal a novel regulatory network in molecular apocrine breast cancers regulated by androgen and AR in which MYC plays a central role as both a key target and a cooperating transcription factor to drive oncogenic growth...
  28. pmc Epithelial cell translocation: New insights into mechanisms of tumor initiation
    Cheuk T Leung
    Department of Cell Biology, Harvard Medical School, Boston, MA, USA
    Bioessays 35:80-3. 2013
    ..This epithelial cell translocation process exerts a selective pressure on early mutant cells to survive and grow in new microenvironment outside of their native niches...
  29. ncbi Cellular heterogeneity and molecular evolution in cancer
    Vanessa Almendro
    Department of Medical Oncology, Dana Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Annu Rev Pathol 8:277-302. 2013
    ..We also discuss experimental approaches that are commonly used to infer intratumor heterogeneity and describe how these methodologies can be translated into clinical practice...
  30. pmc Genomic collaboration of estrogen receptor alpha and extracellular signal-regulated kinase 2 in regulating gene and proliferation programs
    Zeynep Madak-Erdogan
    University of Illinois, Department of Molecular and Integrative Physiology, 407 South Goodwin Ave, Urbana, IL 61801 3704, USA
    Mol Cell Biol 31:226-36. 2011
    ....
  31. pmc Growth factor stimulation induces a distinct ER(alpha) cistrome underlying breast cancer endocrine resistance
    Mathieu Lupien
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Genes Dev 24:2219-27. 2010
    ....
  32. pmc Growth-inhibitory and tumor- suppressive functions of p53 depend on its repression of CD44 expression
    Samuel Godar
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 134:62-73. 2008
    ..They also suggest that the derepression of CD44 resulting from inactivation of p53 can potentially aid the survival of immortalized, premalignant cells...
  33. pmc Systemic endocrine instigation of indolent tumor growth requires osteopontin
    Sandra S McAllister
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 133:994-1005. 2008
    ..These results reveal that outgrowth of indolent tumors can be governed on a systemic level by endocrine factors released by certain instigating tumors, and hold important experimental and therapeutic implications...
  34. ncbi Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis
    Jing Yang
    Department of Pharmacology and Pediatrics, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    Dev Cell 14:818-29. 2008
    ..Studies in both fields are critical for our molecular understanding of cell migration and morphogenesis...
  35. pmc The epithelial-mesenchymal transition generates cells with properties of stem cells
    Sendurai A Mani
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 133:704-15. 2008
    ..These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties...
  36. pmc FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription
    Mathieu Lupien
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Cell 132:958-70. 2008
    ..FoxA1 translates this epigenetic signature into changes in chromatin structure thereby establishing lineage-specific transcriptional enhancers and programs...
  37. ncbi CARM1 regulates estrogen-stimulated breast cancer growth through up-regulation of E2F1
    Seth Frietze
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
    Cancer Res 68:301-6. 2008
    ..These studies identify CARM1 as a potential new target in the treatment of estrogen-dependent breast cancer...
  38. ncbi Adaptation versus selection: the origins of metastatic behavior
    Christina Scheel
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Cancer Res 67:11476-9; discussion 11479-80. 2007
  39. ncbi A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion
    Michael Overholtzer
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 131:966-79. 2007
    ....
  40. pmc Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers
    Sendurai A Mani
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 104:10069-74. 2007
    ..These observations indicate that FOXC2 plays a central role in promoting invasion and metastasis and that it may prove to be a highly specific molecular marker for human basal-like breast cancers...
  41. pmc Functional role and oncogene-regulated expression of the BH3-only factor Bmf in mammary epithelial anoikis and morphogenesis
    Tobias Schmelzle
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:3787-92. 2007
    ..Finally, Bmf is expressed during involution of the mouse mammary gland, suggesting that Bmf may also critically contribute to developmental processes in vivo...
  42. pmc BIM regulates apoptosis during mammary ductal morphogenesis, and its absence reveals alternative cell death mechanisms
    Arnaud A Mailleux
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 12:221-34. 2007
    ..These data provide important mechanistic information on the processes involved in sculpting the mammary gland and demonstrate that BIM is a critical regulator of apoptosis in vivo...
  43. pmc A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer
    Jerome Eeckhoute
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 20:2513-26. 2006
    ....
  44. pmc Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon
    Michael Overholtzer
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:12405-10. 2006
    ....
  45. ncbi p63 regulates an adhesion programme and cell survival in epithelial cells
    Danielle K Carroll
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Nat Cell Biol 8:551-61. 2006
    ..Our results implicate p63 as a key regulator of cellular adhesion and survival in basal cells of the mammary gland and other stratified epithelial tissues...
  46. pmc Unique ERalpha cistromes control cell type-specific gene regulation
    Susan A Krum
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, D730, Boston, Massachusetts 02115, USA
    Mol Endocrinol 22:2393-406. 2008
    ..These results support a model for the cell type-specific action of E2 being driven primarily through specific ERalpha occupancy of epigenetically marked cis-regulatory regions of target genes...
  47. pmc Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen
    Antoni Hurtado
    Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
    Nature 456:663-6. 2008
    ..These data provide mechanistic insight into the molecular basis of endocrine resistance in breast cancer...
  48. pmc The role of the microenvironment in mammary gland development and cancer
    Kornelia Polyak
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cold Spring Harb Perspect Biol 2:a003244. 2010
    ..In this article, we overview the importance of cellular interactions and microenvironmental signals in mammary gland development and cancer...
  49. pmc Concurrent suppression of integrin alpha5, radixin, and RhoA phenocopies the effects of miR-31 on metastasis
    Scott Valastyan
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Cancer Res 70:5147-54. 2010
    ..These findings provide mechanistic insights into the metastatic process and have implications about the importance of pleiotropy for the biological actions of miRNAs...
  50. pmc Stem cells in the human breast
    Ole William Petersen
    Department of Cellular and Molecular Medicine, Faculty of Health Sciences, The Panum Building, University of Copenhagen, DK 2200 Copenhagen N, Denmark
    Cold Spring Harb Perspect Biol 2:a003160. 2010
    ....
  51. pmc Estrogen-dependent and estrogen-independent mechanisms contribute to AIB1-mediated tumor formation
    Maria I Torres-Arzayus
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 70:4102-11. 2010
    ..We therefore conclude that AIB1 can exert its oncogenicity through tissue-specific estrogen-dependent and estrogen-independent functions...
  52. pmc Multimodal regulation of E2F1 gene expression by progestins
    Hilary E Wade
    Duke University Medical Center, Department of Pharmacology and Cancer Biology, Durham, NC 27710, USA
    Mol Cell Biol 30:1866-77. 2010
    ..Taken together, these results suggest a new paradigm for multimodal regulation of target gene expression by PR...
  53. pmc Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen
    Frédéric Bienvenu
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 463:374-8. 2010
    ..Our approach, which we term 'genetic-proteomic', can be used to study the in vivo function of essentially any protein...
  54. pmc YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway
    Jianmin Zhang
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
    Nat Cell Biol 11:1444-50. 2009
    ....
  55. pmc Tumor heterogeneity: causes and consequences
    Andriy Marusyk
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Biochim Biophys Acta 1805:105-17. 2010
    ..Furthermore, we discuss potential biological and clinical implications of intra-tumor clonal heterogeneity...
  56. pmc A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis
    Scott Valastyan
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 137:1032-46. 2009
    ..Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis...
  57. ncbi Cistromics of hormone-dependent cancer
    Mathieu Lupien
    Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA
    Endocr Relat Cancer 16:381-9. 2009
    ..Since this directly impacts signaling through nuclear receptors, these discoveries should significantly impact the development of novel therapeutic strategies directed against multiple types of cancer...
  58. pmc Coactivator function defines the active estrogen receptor alpha cistrome
    Mathieu Lupien
    Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Mol Cell Biol 29:3413-23. 2009
    ..Together, our results suggest that the transcriptional response to E2 in breast cancer cells is dependent on the interplay between polymerase II pre-occupied promoters and the subset of the ERalpha cistrome associated with coactivation...
  59. ncbi Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits
    Kornelia Polyak
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 9:265-73. 2009
    ....
  60. ncbi Epigenetic patterns of embryonic and adult stem cells
    Noga Bloushtain-Qimron
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cell Cycle 8:809-17. 2009
    ....
  61. pmc Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers
    Jerome Eeckhoute
    Universite de Rennes I, CNRS, UMR 6026, Equipe SPARTE, Campus de Beaulieu, 35042 Rennes Cedex, France
    Genome Res 19:372-80. 2009
    ..Mechanisms that restrict the activity of shared FOXA1-bound enhancers likely play a significant role in defining the cell-type-specific functions of FOXA1...
  62. pmc Functional proteomics approach to investigate the biological activities of cDNAs implicated in breast cancer
    Abigail E Witt
    Department of Cell Biology, Harvard Medical School, Boston Massachusetts 02115, USA
    J Proteome Res 5:599-610. 2006
    ....

Research Grants30

  1. Signaling in Inflammation, Stress, and Tumorigenesis
    GEORGE ROBERT STARK; Fiscal Year: 2013
    ..abstract_text> ..