Androgen dependent transcription of a mouse prostatic protein gene, PSP94: involvement of estrogen receptors.

Prostatic secretory protein 94 (PSP94) is a prostatic protein found in both humans and rodents. As with other prostatic proteins, expression of this protein is regulated by androgens. In order to understand the androgen-responsive transcriptional regulation mechanisms involved, the present study aimed to identify and characterize the promoter activity of the gene. The 5'flanking (5'f) region of mouse PSP94 (mPSP94) gene was cloned and introduced into a vector upstream of the luciferase reporter gene. A Chinese hamster ovarian cell line, CHO, and a human prostate adenocarcinoma cell line, LNCaP, were transiently transfected with our reporter constructs along with an androgen receptor expression vector, and treated with dihydrotestosterone. Reporter gene assay revealed that the 5'f region of mPSP94 gene was indeed responsible for the androgen-dependent transcription. Subsequent deletion and mutation analysis indicated that the androgen responsive element (ARE)-like sequence at position -93 from the transcription start site was primarily responsible for androgen dependency. Interestingly, when estrogen receptor (ER) α was co-transfected, the androgen-dependent transcription was substantially increased. However, ERα-dependent enhancement of androgen responses was not observed when estrogen responsive element (ERE)-like motifs of the promoter region were deleted. Administration of estrogen did not influence the enhancement associated with ERα, although an anti-estrogen suppressed such effects. Collectively, these data suggest that the androgen-dependent transcription of the mPSP94 gene was co-regulated/modulated by the presence of ERα via ERE-like motifs.