Cyclin D1 antagonizes BRCA1 repression of estrogen receptor α activity

Chenguang Wang, Saijun Fan, Zhiping Li, Maofu Fu, Mahadev Rao, Yongxian Ma, Michael P. Lisanti, Chris Albanese, Benita S. Katzenellenbogen, Peter J. Kushner, Barbara Weber, Eliot M. Rosen, Richard G. Pestell

Research output: Contribution to journalArticle

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Abstract

The cyclin D1 gene is frequently overexpressed in human breast cancer and is capable of inducing mammary tumorigenesis when overexpressed in transgenic mice. The BRCA1 breast tumor susceptibility gene product inhibits breast cancer cellular growth and the activity of several transcription factors. Herein, cyclin D1 antagonized BRCA1-mediated repression of estrogen receptor α (ERα)-dependent gene expression. Cyclin D1 repression of BRCA1 function was mediated independently of its cyclin-dependent kinase, retinoblastoma protein, or p160 (SRC-1) functions in human breast and prostate cancer cells. In vitro, cyclin D1 competed with BRCA1 for ERα binding. Cyclin D1 and BRCA1 were both capable of binding ERα in a common region of the ERα hinge domain. A novel domain of cyclin D1, predicted to form a helix-loop-helix structure, was required for binding to ERα and for rescue of BRCA1-mediated ERα transcriptional repression. In chromatin immunoprecipitation assays, 17β-estradiol (E2) enhanced ERα and cyclin D1 recruitment to an estrogen response element (ERE). Cyclin D1 expression enhanced ERα recruitment to an ERE. E2 reduced BRCA1 recruitment and BRCA1 expression inhibited E2-induced ERα recruitment at 12 hours. Cyclin D1 expression antagonized BRCA1 inhibition of ERα recruitment to an ERE, providing a mechanism by which cyclin D1 antagonizes BRCA1 function at an ERE. As cyclin D1 abundance is regulated by oncogenic and mitogenic signals, the antagonism of the BRCA1-mediated ERα repression by cyclin D1 may contribute to the selective induction of BRCA1-regulated target genes.

Original languageEnglish
Pages (from-to)6557-6567
Number of pages11
JournalCancer Research
Volume65
Issue number15
DOIs
Publication statusPublished - 01-08-2005

Fingerprint

Cyclin D1
Estrogen Receptors
Response Elements
Estrogens
Breast Neoplasms
bcl-1 Genes
Retinoblastoma Protein
Cyclin-Dependent Kinases
Chromatin Immunoprecipitation
Transgenic Mice
Genes
Estradiol
Prostatic Neoplasms
Carcinogenesis
Breast
Transcription Factors
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Wang, Chenguang ; Fan, Saijun ; Li, Zhiping ; Fu, Maofu ; Rao, Mahadev ; Ma, Yongxian ; Lisanti, Michael P. ; Albanese, Chris ; Katzenellenbogen, Benita S. ; Kushner, Peter J. ; Weber, Barbara ; Rosen, Eliot M. ; Pestell, Richard G. / Cyclin D1 antagonizes BRCA1 repression of estrogen receptor α activity. In: Cancer Research. 2005 ; Vol. 65, No. 15. pp. 6557-6567.
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abstract = "The cyclin D1 gene is frequently overexpressed in human breast cancer and is capable of inducing mammary tumorigenesis when overexpressed in transgenic mice. The BRCA1 breast tumor susceptibility gene product inhibits breast cancer cellular growth and the activity of several transcription factors. Herein, cyclin D1 antagonized BRCA1-mediated repression of estrogen receptor α (ERα)-dependent gene expression. Cyclin D1 repression of BRCA1 function was mediated independently of its cyclin-dependent kinase, retinoblastoma protein, or p160 (SRC-1) functions in human breast and prostate cancer cells. In vitro, cyclin D1 competed with BRCA1 for ERα binding. Cyclin D1 and BRCA1 were both capable of binding ERα in a common region of the ERα hinge domain. A novel domain of cyclin D1, predicted to form a helix-loop-helix structure, was required for binding to ERα and for rescue of BRCA1-mediated ERα transcriptional repression. In chromatin immunoprecipitation assays, 17β-estradiol (E2) enhanced ERα and cyclin D1 recruitment to an estrogen response element (ERE). Cyclin D1 expression enhanced ERα recruitment to an ERE. E2 reduced BRCA1 recruitment and BRCA1 expression inhibited E2-induced ERα recruitment at 12 hours. Cyclin D1 expression antagonized BRCA1 inhibition of ERα recruitment to an ERE, providing a mechanism by which cyclin D1 antagonizes BRCA1 function at an ERE. As cyclin D1 abundance is regulated by oncogenic and mitogenic signals, the antagonism of the BRCA1-mediated ERα repression by cyclin D1 may contribute to the selective induction of BRCA1-regulated target genes.",
author = "Chenguang Wang and Saijun Fan and Zhiping Li and Maofu Fu and Mahadev Rao and Yongxian Ma and Lisanti, {Michael P.} and Chris Albanese and Katzenellenbogen, {Benita S.} and Kushner, {Peter J.} and Barbara Weber and Rosen, {Eliot M.} and Pestell, {Richard G.}",
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Wang, C, Fan, S, Li, Z, Fu, M, Rao, M, Ma, Y, Lisanti, MP, Albanese, C, Katzenellenbogen, BS, Kushner, PJ, Weber, B, Rosen, EM & Pestell, RG 2005, 'Cyclin D1 antagonizes BRCA1 repression of estrogen receptor α activity', Cancer Research, vol. 65, no. 15, pp. 6557-6567. https://doi.org/10.1158/0008-5472.CAN-05-0486

Cyclin D1 antagonizes BRCA1 repression of estrogen receptor α activity. / Wang, Chenguang; Fan, Saijun; Li, Zhiping; Fu, Maofu; Rao, Mahadev; Ma, Yongxian; Lisanti, Michael P.; Albanese, Chris; Katzenellenbogen, Benita S.; Kushner, Peter J.; Weber, Barbara; Rosen, Eliot M.; Pestell, Richard G.

In: Cancer Research, Vol. 65, No. 15, 01.08.2005, p. 6557-6567.

Research output: Contribution to journalArticle

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T1 - Cyclin D1 antagonizes BRCA1 repression of estrogen receptor α activity

AU - Wang, Chenguang

AU - Fan, Saijun

AU - Li, Zhiping

AU - Fu, Maofu

AU - Rao, Mahadev

AU - Ma, Yongxian

AU - Lisanti, Michael P.

AU - Albanese, Chris

AU - Katzenellenbogen, Benita S.

AU - Kushner, Peter J.

AU - Weber, Barbara

AU - Rosen, Eliot M.

AU - Pestell, Richard G.

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Y1 - 2005/8/1

N2 - The cyclin D1 gene is frequently overexpressed in human breast cancer and is capable of inducing mammary tumorigenesis when overexpressed in transgenic mice. The BRCA1 breast tumor susceptibility gene product inhibits breast cancer cellular growth and the activity of several transcription factors. Herein, cyclin D1 antagonized BRCA1-mediated repression of estrogen receptor α (ERα)-dependent gene expression. Cyclin D1 repression of BRCA1 function was mediated independently of its cyclin-dependent kinase, retinoblastoma protein, or p160 (SRC-1) functions in human breast and prostate cancer cells. In vitro, cyclin D1 competed with BRCA1 for ERα binding. Cyclin D1 and BRCA1 were both capable of binding ERα in a common region of the ERα hinge domain. A novel domain of cyclin D1, predicted to form a helix-loop-helix structure, was required for binding to ERα and for rescue of BRCA1-mediated ERα transcriptional repression. In chromatin immunoprecipitation assays, 17β-estradiol (E2) enhanced ERα and cyclin D1 recruitment to an estrogen response element (ERE). Cyclin D1 expression enhanced ERα recruitment to an ERE. E2 reduced BRCA1 recruitment and BRCA1 expression inhibited E2-induced ERα recruitment at 12 hours. Cyclin D1 expression antagonized BRCA1 inhibition of ERα recruitment to an ERE, providing a mechanism by which cyclin D1 antagonizes BRCA1 function at an ERE. As cyclin D1 abundance is regulated by oncogenic and mitogenic signals, the antagonism of the BRCA1-mediated ERα repression by cyclin D1 may contribute to the selective induction of BRCA1-regulated target genes.

AB - The cyclin D1 gene is frequently overexpressed in human breast cancer and is capable of inducing mammary tumorigenesis when overexpressed in transgenic mice. The BRCA1 breast tumor susceptibility gene product inhibits breast cancer cellular growth and the activity of several transcription factors. Herein, cyclin D1 antagonized BRCA1-mediated repression of estrogen receptor α (ERα)-dependent gene expression. Cyclin D1 repression of BRCA1 function was mediated independently of its cyclin-dependent kinase, retinoblastoma protein, or p160 (SRC-1) functions in human breast and prostate cancer cells. In vitro, cyclin D1 competed with BRCA1 for ERα binding. Cyclin D1 and BRCA1 were both capable of binding ERα in a common region of the ERα hinge domain. A novel domain of cyclin D1, predicted to form a helix-loop-helix structure, was required for binding to ERα and for rescue of BRCA1-mediated ERα transcriptional repression. In chromatin immunoprecipitation assays, 17β-estradiol (E2) enhanced ERα and cyclin D1 recruitment to an estrogen response element (ERE). Cyclin D1 expression enhanced ERα recruitment to an ERE. E2 reduced BRCA1 recruitment and BRCA1 expression inhibited E2-induced ERα recruitment at 12 hours. Cyclin D1 expression antagonized BRCA1 inhibition of ERα recruitment to an ERE, providing a mechanism by which cyclin D1 antagonizes BRCA1 function at an ERE. As cyclin D1 abundance is regulated by oncogenic and mitogenic signals, the antagonism of the BRCA1-mediated ERα repression by cyclin D1 may contribute to the selective induction of BRCA1-regulated target genes.

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