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
• Yang XH, Richardson AL, Torres-Arzayus MI, Zhou P, Sharma C, Kazarov AR, Andzelm MM, Strominger JL, Brown M, Hemler ME.CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization.Cancer Res 2008 May 1;68(
  18451146
• Li W, Carroll JS, Brown M, Liu S.xMAN: extreme MApping of OligoNucleotides.BMC Genomics 2008;9 Suppl 1:S20.
  18366610
• Tan-Wong SM, French JD, Proudfoot NJ, Brown MA.Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene.Proc Natl Acad Sci U S A 2008 Apr 1;105(13):5160-5.
  18375767
• Spurdle AB, Lakhani SR, Healey S, Parry S, Da Silva LM, Brinkworth R, Hopper JL, Brown MA, Babikyan D, Chenevix-Trench G, Tavtigian SV, Goldgar DE.Clinical classification of BRCA1 and BRCA2 DNA sequence variants: the value of cytokeratin profiles and evol
  18375895
• Lupien M, Eeckhoute J, Meyer CA, Wang Q, Zhang Y, Li W, Carroll JS, Liu XS, Brown M.FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription.Cell 2008 Mar 21;132(6):958-70.
  18358809
• Faddy HM, Smart CE, Xu R, Lee GY, Kenny PA, Feng M, Rao R, Brown MA, Bissell MJ, Roberts-Thomson SJ, Monteith GR.Localization of plasma membrane and secretory calcium pumps in the mammary gland.Biochem Biophys Res Commun 2008 May 9;369(3):977-81.
  18334228
• Johnson DS, Li W, Gordon DB, Bhattacharjee A, Curry B, Ghosh J, Brizuela L, Carroll JS, Brown M, Flicek P, Koch CM, Dunham I, Bieda M, Xu X, Farnham PJ, Kapranov P, Nix DA, Gingeras TR, Zhang X, Holster H, Jiang N, Green RD, Song JS, McCuine SA, Anton E,
  18258921
• Krum SA, Miranda-Carboni GA, Hauschka PV, Carroll JS, Lane TF, Freedman LP, Brown M.Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival.EMBO J 2008 Feb 6;27(3):535-45.
  18219273
• Frietze S, Lupien M, Silver PA, Brown M.CARM1 regulates estrogen-stimulated breast cancer growth through up-regulation of E2F1.Cancer Res 2008 Jan 1;68(1):301-6.
  18172323
• Wang Q, Li W, Liu XS, Carroll JS, Jänne OA, Keeton EK, Chinnaiyan AM, Pienta KJ, Brown M.A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth.Mol Cell 2007 Aug 3;27(3):380-92.
  17679089
• Eeckhoute J, Keeton EK, Lupien M, Krum SA, Carroll JS, Brown M.Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer.Cancer Res 2007 Jul 1;67(13):6477-83.
  17616709
• Harvey TJ, Henderson A, Gazi E, Clarke NW, Brown M, Faria EC, Snook RD, Gardner P.Discrimination of prostate cancer cells by reflection mode FTIR photoacoustic spectroscopy.Analyst 2007 Apr;132(4):292-5.
  17554407
• Kaplan L, Brown MA.The transition of nurse practitioners to changes in prescriptive authority.J Nurs Scholarsh 2007;39(2):184-90.
  17535320
• Clarke NW, Brown MD.The Influence of Lipid Metabolism on Prostate Cancer Development and Progression: Is it Time for a Closer Look?.Eur Urol 2007 Apr 20.
  17467164
• O'Mahony D, Morris JC, Quinn C, Gao W, Wilson WH, Gause B, Pittaluga S, Neelapu S, Brown M, Fleisher TA, Gulley JL, Schlom J, Nussenblatt R, Albert P, Davis TA, Lowy I, Petrus M, Waldmann TA, Janik JE.A pilot study of CTLA-4 blockade after cancer vaccine
  17289891
• Gazi E, Dwyer J, Lockyer NP, Gardner P, Shanks JH, Roulson J, Hart CA, Clarke NW, Brown MD.Biomolecular profiling of metastatic prostate cancer cells in bone marrow tissue using FTIR microspectroscopy: a pilot study.Anal Bioanal Chem 2007 Mar;387(5):1621-
  17268776
• Yabroff KR, Davis WW, Lamont EB, Fahey A, Topor M, Brown ML, Warren JL.Patient time costs associated with cancer care.Journal of the National Cancer Institute 2007 Jan 3;99(1):14-23.
  17202109
• Brown MW, Brooks JP, Albert PS, Poggi MM.An analysis of erectile function after intensity modulated radiation therapy for localized prostate carcinoma.Prostate Cancer Prostatic Dis 2006 Dec 26.
  17189954
• Carroll DK, Carroll JS, Leong CO, Cheng F, Brown M, Mills AA, Brugge JS, Ellisen LW.p63 regulates an adhesion programme and cell survival in epithelial cells.Nat Cell Biol 2006 Jun;8(6):551-61.
  16715076
• De Roos AJ, Rothman N, Brown M, Bell DA, Pittman GS, Shapiro WR, Selker RG, Fine HA, Black PM, Inskip PD.Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of adult brain tumors.Neuro-oncol 2006 Apr;8(2):145-55.
  16598069
• Lewis AG, Flanagan J, Marsh A, Pupo GM, Mann G, Spurdle AB, Lindeman GJ, Visvader JE, Brown MA, Chenevix-Trench G,.Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer.Breast Cancer Res 2005;7(6):R1005-16.
  16280053
• Tesoriero AA, Wong EM, Jenkins MA, Hopper JL, Brown MA, Chenevix-Trench G, Spurdle AB, Southey MC,.Molecular characterization and cancer risk associated with BRCA1 and BRCA2 splice site variants identified in multiple-case breast cancer families.Hum Mutat
  16211554
• Febbo PG, Lowenberg M, Thorner AR, Brown M, Loda M, Golub TR.Androgen mediated regulation and functional implications of fkbp51 expression in prostate cancer.J Urol 2005 May;173(5):1772-7.
  15821585
• Hestermann EV, Brown M.Agonist and chemopreventative ligands induce differential transcriptional cofactor recruitment by aryl hydrocarbon receptor.Mol Cell Biol 2003 Nov;23(21):7920-5.
  14560034
• Carroll PR, Kantoff PW, Balk SP, Brown MA, D'amico AV, George DJ, Grossfeld GD, Johnson CS, Kelly WK, Klotz L, Lee WR, Lubeck DP, Mcleod DG, Oh WK, Pollack A, Sartor O, Smith MR, Hart C,.Overview consensus statement. Newer approaches to androgen deprivati
  12231036
• Shang Y, Myers M, Brown M.Formation of the androgen receptor transcription complex.Mol Cell 2002 Mar;9(3):601-10.
  11931767
• Shang Y, Brown M.Molecular determinants for the tissue specificity of SERMs.Science 2002 Mar 29;295(5564):2465-8.
  11923541
• Haiman CA, Hankinson SE, Spiegelman D, Brown M, Hunter DJ.No association between a single nucleotide polymorphism in CYP19 and breast cancer risk.Cancer Epidemiol Biomarkers Prev 2002 Feb;11(2):215-6.
  11867511
• Haiman CA, Brown M, Hankinson SE, Spiegelman D, Colditz GA, Willett WC, Kantoff PW, Hunter DJ.The androgen receptor CAG repeat polymorphism and risk of breast cancer in the Nurses' Health Study.Cancer Res 2002 Feb 15;62(4):1045-9.
  11861380
• DiRenzo J, Signoretti S, Nakamura N, Rivera-Gonzalez R, Sellers W, Loda M, Brown M.Growth factor requirements and basal phenotype of an immortalized mammary epithelial cell line.Cancer Res 2002 Jan 1;62(1):89-98.
  11782364
• Yahata T, Shao W, Endoh H, Hur J, Coser KR, Sun H, Ueda Y, Kato S, Isselbacher KJ, Brown M, Shioda T.Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein.Genes Dev 2001 Oct 1;15(19):2598-612.
  11581164
• Rebbeck TR, Wang Y, Kantoff PW, Krithivas K, Neuhausen SL, Godwin AK, Daly MB, Narod SA, Brunet JS, Vesprini D, Garber JE, Lynch HT, Weber BL, Brown M.Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history
  11454686
• Jones GB, Hynd G, Wright JM, Purohit A, Plourde GW, Huber RS, Mathews JE, Li A, Kilgore MW, Bubley GJ, Yancisin M, Brown MA.Target-directed enediynes: designed estramycins.J Org Chem 2001 Jun 1;66(11):3688-95.
  11374986
• Planas-Silva MD, Shang Y, Donaher JL, Brown M, Weinberg RA.AIB1 enhances estrogen-dependent induction of cyclin D1 expression.Cancer Res 2001 May 15;61(10):3858-62.
  11358796
• Shang Y, Hu X, DiRenzo J, Lazar MA, Brown M.Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription.Cell 2000 Dec 8;103(6):843-52.
  11136970
• Haiman CA, Hankinson SE, Spiegelman D, Colditz GA, Willett WC, Speizer FE, Brown M, Hunter DJ.Polymorphic repeat in AIB1 does not alter breast cancer risk.Breast Cancer Res 2000;2(5):378-85.
  11056690
• Krithivas K, Yurgalevitch SM, Mohr BA, Wilcox CJ, Batter SJ, Brown M, Longcope C, McKinlay JB, Kantoff PW.Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men.J Endocrinol 19
  10396030
• Hanstein B, Liu H, Yancisin MC, Brown M.Functional analysis of a novel estrogen receptor-beta isoform.Mol Endocrinol 1999 Jan;13(1):129-37.
  9892018
• Shim WS, DiRenzo J, DeCaprio JA, Santen RJ, Brown M, Jeng MH.Segregation of steroid receptor coactivator-1 from steroid receptors in mammary epithelium.Proc Natl Acad Sci U S A 1999 Jan 5;96(1):208-13.
  9874797
• Febbo PG, Kantoff PW, Giovannucci E, Brown M, Chang G, Hennekens CH, Stampfer M.Debrisoquine hydroxylase (CYP2D6) and prostate cancer.Cancer Epidemiol Biomarkers Prev 1998 Dec;7(12):1075-8.
  9865424
• Giovannucci E, Stampfer MJ, Krithivas K, Brown M, Dahl D, Brufsky A, Talcott J, Hennekens CH, Kantoff PW.The CAG repeat within the androgen receptor gene and its relationship to prostate cancer.Proc Natl Acad Sci U S A 1997 Apr 1;94(7):3320-3.
  9096391
• Kantoff PW, Febbo PG, Giovannucci E, Krithivas K, Dahl DM, Chang G, Hennekens CH, Brown M, Stampfer MJ.A polymorphism of the 5 alpha-reductase gene and its association with prostate cancer: a case-control analysis.Cancer Epidemiol Biomarkers Prev 1997 Mar
  9138662
• Hanstein B, Eckner R, DiRenzo J, Halachmi S, Liu H, Searcy B, Kurokawa R, Brown M.p300 is a component of an estrogen receptor coactivator complex.Proc Natl Acad Sci U S A 1996 Oct 15;93(21):11540-5.
  8876171
• Halachmi S, Marden E, Martin G, MacKay H, Abbondanza C, Brown M.Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription.Science 1994 Jun 3;264(5164):1455-8.
  8197458
• Cherington V, Brown M, Paucha E, St Louis J, Spiegelman BM, Roberts TM.Separation of simian virus 40 large-T-antigen-transforming and origin-binding functions from the ability to block differentiation.Mol Cell Biol 1988 Mar;8(3):1380-4.
  2835674
• Bikel I, Montano X, Agha ME, Brown M, McCormack M, Boltax J, Livingston DM.SV40 small t antigen enhances the transformation activity of limiting concentrations of SV40 large T antigen.Cell 1987 Jan 30;48(2):321-30.
  3026642