DF/HCC Program Affiliation

Cancer Epidemiology
Prostate Cancer
Breast Cancer

DF/HCC Associations

Member, Web Advisory

Research Abstract

Estrogen plays a critical role in the development of the normal breast and in breast cancer. The biochemical mechanisms underlying these processes, however, remain largely unknown. The overall aim of our current research is to build on recent advances in the molecular understanding of estrogen receptor (ER) action to better define the role played by estrogen in the normal breast and in breast cancer. Over the past few years several important coregulatory molecules that play a central role in mediating the transcriptional activity of ER have been identified by several labs including our own. Our current hypothesis is that the differential expression of these molecules accounts in part for the tissue specific activity of selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene. In addition, the gene encoding one of these ER coactivators, AIB1, was cloned as a gene Amplified In Breast cancer raising the possibility that altered expression of an ER coactivator may play a central role in estrogen-stimulated breast cancer growth.
Our work will provide a better understanding of the role played by alterations in estrogen signaling in breast cancer. Identification of those factors which are markers for these changes are likely to lead to the development of better diagnostic and predictive tools. More importantly, the identification of the factors which are the critical regulators of the alterations in estrogen signaling will become new therapeutic targets and may lead to the development of improved strategies for the prevention and treatment of breast cancer.

Publications

• Torres-Arzayus MI, Yuan J, DellaGatta JL, Lane H, Kung AL, Brown M.Targeting the AIB1 oncogene through mammalian target of rapamycin inhibition in the mammary gland.Cancer Res 2006 Dec 1;66(23):11381-8.
  17145884
• Carroll JS, Meyer CA, Song J, Li W, Geistlinger TR, Eeckhoute J, Brodsky AS, Keeton EK, Fertuck KC, Hall GF, Wang Q, Bekiranov S, Sementchenko V, Fox EA, Silver PA, Gingeras TR, Liu XS, Brown M.Genome-wide analysis of estrogen receptor binding sites.Nat G
  17013392
• Eeckhoute J, Carroll JS, Geistlinger TR, Torres-Arzayus MI, Brown M.A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer.Genes Dev 2006 Sep 15;20(18):2513-26.
  16980581
• Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S.X chromosomal abnormalities in basal-like human breast cancer.Cancer Cell 2006 Feb;9(2):121-32.
  16473279
• Come SE, Buzdar AU, Ingle JN, Arteaga CL, Brown M, Dowsett M, Hilsenbeck SG, Kumar R, Johnston SR, Lee AV, Paik S, Pritchard KI, Winer EP, Hart C.Proceedings of the Fifth International Conference on Recent Advances and Future Directions in Endocrine Thera
  16467115
• Jackson EL, Olive KP, Tuveson DA, Bronson R, Crowley D, Brown M, Jacks T.The differential effects of mutant p53 alleles on advanced murine lung cancer.Cancer Res 2005 Nov 15;65(22):10280-8.
  16288016
• Colilla S, Kantoff PW, Neuhausen SL, Godwin AK, Daly MB, Narod SA, Garber JE, Lynch HT, Brown M, Weber BL, Rebbeck TR.The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers.Carcinogenesis 2006 Mar;27(3):599-605.
  16244359
• Wang Q, Carroll JS, Brown M.Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking.Mol Cell 2005 Sep 2;19(5):631-42.
  16137620
• Carroll JS, Liu XS, Brodsky AS, Li W, Meyer CA, Szary AJ, Eeckhoute J, Shao W, Hestermann EV, Geistlinger TR, Fox EA, Silver PA, Brown M.Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA
  16009131
• Torres-Arzayus MI, De Mora JF, Yuan J, Vazquez F, Bronson R, Rue M, Sellers WR, Brown M.High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene.Cancer Cell 2004 Sep;6(3):263-74.
  15380517
• Shao W, Keeton EK, McDonnell DP, Brown M.Coactivator AIB1 links estrogen receptor transcriptional activity and stability.Proc Natl Acad Sci U S A 2004 Aug 2.
  15289619