title: ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells.
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.
authors.affiliation: Department of Biology and Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, GA 30314, United States.
authors.forename: Shravan Kumar
authors.initials: SK
authors.lastname: Komaragiri
authors.affiliation: Department of Biology and Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, GA 30314, United States.
authors.forename: Dhanushka H
authors.initials: DH
authors.lastname: Bostanthirige
authors.affiliation: Department of Biology and Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, GA 30314, United States.
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Morton
authors.affiliation: Department of Biology and Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, GA 30314, United States.
authors.forename: Divya
authors.initials: D
authors.lastname: Patel
authors.affiliation: Department of Biology and Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, GA 30314, United States.
authors.forename: Jugal
authors.initials: J
authors.lastname: Joshi
authors.affiliation: Department of Biology and Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, GA 30314, United States.
authors.forename: Sunil
authors.initials: S
authors.lastname: Upadhyay
authors.affiliation: Department of Biology and Center for Cancer Research and Therapeutics Development, Clark Atlanta University, Atlanta, GA 30314, United States. Electronic address: jchaudhary@cau.edu.
authors.forename: Jaideep
authors.initials: J
authors.lastname: Chaudhary
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics*; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics*; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D000099159:Tacrolimus Binding Protein 5
chemical_list: D051796:Inhibitor of Differentiation Proteins; D011944:Receptors, Androgen; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C410798:AR protein, human; C490128:ID4 protein, human
keywords: ADT; AR; Apoptosis; Cancer; FKBP51; ID4; Migration; bHLH; p21