Journal
CANCER RESEARCH
Volume 67, Issue 24, Pages 11789-11797Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-07-2721
Keywords
-
Categories
Funding
- NCI NIH HHS [CA87986, CA94143, CA96844, CA99163, CA99900, 1U54 CA119341-01, CA76118, CA81076] Funding Source: Medline
Ask authors/readers for more resources
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 (RAT) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available