ACTR/AIB1 functions as an E2F1 coactivator to promote breast cancer cell proliferation and antiestrogen resistance

Maggie C. Louie, June X Zou, Alina Rabinovich, Hongwu Chen

Research output: Contribution to journalArticle

207 Citations (Scopus)

Abstract

Overexpression or amplification of ACTR (also named AIBI, RAC3, p/CIP, TRAM-1, and SRC-3), a member of the p160 family of coactivators for nuclear hormone receptors, has been frequently detected in multiple types of human tumors, including breast cancer. However, its role in cancer cell proliferation and the underlying mechanism are unclear. Here, we show that overexpression of ACTR not only enhances estrogen-stimulated cell proliferation but also, more strikingly, completely negates the cell cycle arrest effect by tamoxifen and pure anti-estrogens. Unexpectedly, we found that ACTR directly interacts, through its N-terminal domain, with E2F1 and is recruited to E2F target gene promoters. Elevation of ACTR in quiescent cells strongly stimulates the transcription of a subset of E2F-responsive genes that are associated with the G1/S transition. We also demonstrated, by adenovirus vector-mediated RNA interference, that ACTR is required for E2F1-mediated gene expression and the proliferation of estrogen receptor (ER)-negative breast cancer cells. Moreover, the ability of elevated ACTR to promote estrogen-independent cell proliferation depends on the function of E2F1 and the association between ACTR and E2F1, but not ER. Thus, our results reveal an essential role of ACTR in control of breast cancer cell proliferation and implicate the ACTR-E2F1 pathway as a novel mechanism in antiestrogen resistance.

Original languageEnglish (US)
Pages (from-to)5157-5171
Number of pages15
JournalMolecular and Cellular Biology
Volume24
Issue number12
DOIs
StatePublished - Jun 2004

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Estrogen Receptor Modulators
Cell Proliferation
Breast Neoplasms
Estrogens
Estrogen Receptors
Aptitude
Tamoxifen
Cytoplasmic and Nuclear Receptors
RNA Interference
Cell Cycle Checkpoints
Adenoviridae
Genes
Neoplasms
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

ACTR/AIB1 functions as an E2F1 coactivator to promote breast cancer cell proliferation and antiestrogen resistance. / Louie, Maggie C.; Zou, June X; Rabinovich, Alina; Chen, Hongwu.

In: Molecular and Cellular Biology, Vol. 24, No. 12, 06.2004, p. 5157-5171.

Research output: Contribution to journalArticle

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