Regulation of bcl-2 expression by dihydrotestosterone in hormone sensitive LNCaP-FGC prostate cancer cells

被引:25
作者
Bruckheimer, EM [1 ]
Spurgers, K
Weigel, NL
Logothetis, C
McDonnell, TJ
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA
[3] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
关键词
prostate; testosterone; prostatic neoplasms; genes; bcl-2; gene expression;
D O I
10.1097/01.ju.0000055140.91204.c7
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Up-regulation of the anti-apoptotic bcl-2 proto-oncogene is associated with androgen independent prostate cancer progression. This observation suggests that the expression of bcl-2 may be negatively regulated by androgens in prostate cancer cells. Materials and Methods: The expression of the proto-oncogene bcl-2 was assessed in the hormone sensitive prostate cancer cell line LNCaP-FGC in the presence and absence of a physiological concentration of 1 nM. dihydrotestosterone (DHT). Sequence analysis of the bcl-2 promoter regions demonstrated the presence of 2 potential androgen response elements. Transient transfections of luciferase reporter constructs containing these potential androgen response elements into LNCaP-FGC cells in the presence and absence of DHT were performed. Steady-state transcripts of bcl-2 were assessed using RNase protection assays. Results: Cells cultured in charcoal stripped serum in the presence of DHT resulted in downregulation of bcl-2 protein. Down-regulation of bcl-2 protein and mRNA by DHT was inhibited by coincubation with the antiandrogen bicalutamide, an agent that competitively inhibits binding of DHT to androgen receptor. Luciferase reporter constructs containing candidate androgen response elements were transrepressed in the presence of DHT. Bcl-2 mRNA was also downregulated by DHT and this down-regulation could not be abolished by cycloheximide. Conclusions: Together these results suggest that the suppression of bcl-2 expression by DHT in hormone sensitive LNCaP-FGC prostate cancer cells occurs directly. In addition, these results provide a possible mechanistic basis for the up-regulation (derepression) of bcl-2 observed in hormone independent prostate cancers.
引用
收藏
页码:1553 / 1557
页数:5
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