Androgen receptor auto-regulates its expression by a negative feedback loop through upregulation of IFI16 protein.
Expression of androgen receptor (AR) in prostate epithelial cells is thought to regulate cell proliferation, differentiation, and survival. However, the molecular mechanisms remain unclear. We report that re-expression of AR in PC-3 human prostate cancer cell line resulted in upregulation of IFI16 protein, a negative regulator of cell growth. We found that the IFI16 protein bound to AR in a ligand-dependent manner and the DNA-binding domain (DBD) of the AR was sufficient to bind IFI16. Furthermore, re-expression of IFI16 protein in LNCaP prostate cancer cells, which do not express IFI16 protein, resulted in downregulation of AR expression and an inhibition of the expression of AR target genes. Our observations identify a role for IFI16 protein in AR-mediated functions.
Department of Radiation Oncology, Loyola University Chicago and Edward Hines Jr. VA Hospital, 5th Avenue and Roosevelt Road, Building #1, Mail Code 114B, Hines, IL 60141, USA.
Fatouma
F
Alimirah
Jianming
J
Chen
Hong
H
Xin
Divaker
D
Choubey
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
D009687:Nuclear Proteins; D010750:Phosphoproteins; D011944:Receptors, Androgen; C076700:IFI16 protein, human