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Biochem Biophys Res Commun. 2016 Sep 9;478(1):60-66. doi: 10.1016/j.bbrc.2016.07.092. Epub 2016 Jul 25.

ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells.

Author information

1
Department of Biology and Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, GA 30314, United States.
2
Department of Biology and Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, GA 30314, United States. Electronic address: jchaudhary@cau.edu.

Abstract

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, we examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function.

KEYWORDS:

ADT; AR; Apoptosis; Cancer; FKBP51; ID4; Migration; bHLH; p21

PMID:
27462022
PMCID:
PMC4991035
DOI:
10.1016/j.bbrc.2016.07.092
[Indexed for MEDLINE]
Free PMC Article

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