Transcriptional regulation of the TGF-beta1 promoter by androgen receptor.
TGF (transforming growth factor)-beta1 is a multifunctional cytokine that influences homoeostatic processes of various tissues. TGF-beta1 expression is inhibited by androgens in the prostate gland, whereas its expression is enhanced by androgens in highly metastatic prostate cancer cells. Here, we examined regulation of human TGF-beta1 promoter activity by androgen in prostate cancer cells. The full-length (-3363 to +110) promoter showed a high level of activity in response to androgen in PC3mm2 cells expressing AR (androgen receptor). Further deletion analysis revealed three distal and three proximal AREs (androgen-response elements) in the promoter. Gel-shift and footprint assays show that these AREs physically interact with the DNA-binding domain of AR. Chromatin immunoprecipitation assays revealed the androgen-dependent recruitment of AR to the ARE-containing regions of the TGF-beta1 gene. More importantly, a negative ARE was detected in the TGF-beta1 promoter. Both positive and negative AREs are functional in the androgen-regulated transcription of the TGF-beta1 promoter. These findings imply that androgen signalling may positively or negatively regulate TGF-beta1 expression in response to various signals or under different environmental conditions.
Qi
Wei
W
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030-4009, USA.
Gao
Shen
S
Wang
Zhengxin
Z
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D016415:Sequence Alignment; D015398:Signal Transduction; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
C410798:AR protein, human; D011944:Receptors, Androgen; D053773:Transforming Growth Factor beta1