p53 overexpression represses androgen-mediated induction of NKX3.1 in a prostate cancer cell line.
- Author:
Anli JIANG
1
;
Chunxiao YU
;
Pengju ZHANG
;
Weiwen CHEN
;
Wenwen LIU
;
Xiaoyan HU
;
Jianye ZHANG
Author Information
1. Department of Biochemistry, Medical School of Shandong University, Jinan 250012, China. Zhjy@sdu.edu.cn
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
androgens;
gene expression regulation;
NKX3.1 protein;
human;
prostate neoplasms;
p53
- MeSH:
Tumor Suppressor Protein p53/genetics/*metabolism;
Transcription Factors/genetics/*metabolism;
Trans-Activation (Genetics)/drug effects;
Response Elements;
RNA, Messenger/genetics;
Prostatic Neoplasms/genetics/*metabolism;
Promoter Regions (Genetics)/genetics;
Plasmids/genetics;
Male;
Humans;
Homeodomain Proteins/genetics/*metabolism;
Genes, Reporter/genetics;
Down-Regulation;
Cell Line, Tumor;
Androgens/*pharmacology
- From:Experimental & Molecular Medicine
2006;38(6):625-633
- CountryRepublic of Korea
- Language:English
-
Abstract:
Prostate cancer is a disease involving complicated multiple-gene alterations. Both NKX3.1 and p53 are related to prostate cancer and play crucial roles in prostate cancer progression. However, little is known about the relationships and interactions between p53 and NKX3.1 in prostate cancer. We found that NKX3.1 expression is down-regulated by over-expression of wild type (wt) p53 in prostate cancer LNCaP cells. NKX3.1 is down-regulated at both the mRNA and protein levels by p53 over- expression due to either transient transfection of exogenous p53 or induction of endogenous p53. p53 over-expression represses androgen-induced transactivation of NKX3.1 by inhibiting the promoter of the androgen acceptor (AR) gene and by blocking AR-DNA binding activity. In addition, transfection with the p21 expression vector (pPSA-p21) showed that p21 does not reduce NKX3.1 expression, indicating that NKX3.1 expression is not the result of nonspecific effects of cell growth arrest. Our results provide biochemical and cellular biologic evidence that NKX3.1 is down-regulated by p53 over-expression in prostate cancer cells.
