Ada3 requirement for HAT recruitment to estrogen receptors and estrogen-dependent breast cancer cell proliferation

Aleksandra Germaniuk-Kurowska, Alo Nag, Xiangshan Zhao, Manjari Dimri, Hamid Band, Vimla Band

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

We have previously shown that evolutionarily conserved alteration/ deficiency in activation (Ada) protein associates with and promotes estrogen receptor (ER)-mediated target gene expression. Here, we examined the role of endogenous Ada3 to recruit histone acetyl transferases (HAT) to an ER-responsive promoter and its role in estrogen-dependent cell proliferation and malignant phenotype. Using a combination of glycerol gradient cosedimentation and immunoprecipitation analyses, we show that Ada3, ER, and three distinct HATs [p300, (p300/CBP-associated factor) PCAF, and general control nonrepressed 5 (Gcn5)] are present in a complex. Using chromatin immunoprecipitation analysis, we show that short hairpin RNA (shRNA)-mediated knockdown of Ada3 in ER-positive breast cancer cells significantly reduced the ligand-dependent recruitment of p300, PCAF, and Gcn5 to the ER-responsive pS2 promoter. Finally, we use shRNA knockdown to show that Ada3 is critical for estrogen-dependent proliferation of ER-positive breast cancer cell lines in two-dimensional, as well as three-dimensional, culture. Knockdown of Ada3 in ER-positive MCF-7 cells induced reversion of the transformed phenotype in three-dimensional culture. Thus, our results show an important role of Ada3 in HAT recruitment to estrogen-responsive target gene promoters and for estrogen-dependent proliferation of breast cancer cells.

Original languageEnglish (US)
Pages (from-to)11789-11797
Number of pages9
JournalCancer Research
Volume67
Issue number24
DOIs
StatePublished - Dec 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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