STEROID-INVOLVED TRANSCRIPTIONAL REGULATION OF HUMAN GENES ENCODING PROSTATIC ACID-PHOSPHATASE, PROSTATE-SPECIFIC ANTIGEN, AND PROSTATE-SPECIFIC GLANDULAR KALLIKREIN

We have compared the steroid regulation of human genes encoding prosta tic acid phosphatase (hPAP), prostate-specific antigen (hPSA), and pro state-specific glandular kallikrein (hK2) at the level of transcriptio n. Reporter constructs of hPAP promoter covering the region -734/+467 were functional in both prostatic (LNCaP and PC-3) and nonprostatic (C V-1) cell lines in transient transfections. hPAP -231/+50 with eight i dentified transcription factor-binding sites showed the highest, and h PAP -734/+467 showed the lowest transcriptional activity in CV-1 cells . The hPAP promoter could not be induced with androgen, glucocorticoid , or progesterone, contrary to the hPSA (-620/+40) and hK2 (-493/+27) promoters in PC-3 cells cotransfected with the respective steroid rece ptor expression vector. Therefore, steroids cannot directly regulate h PAP gene expression via receptor binding to steroid response elements at -178 and +336, which have been shown to have androgen receptor-bind ing ability in vitro. Glucocorticoid was the most powerful activator o f the hPSA construct at 10-nM steroid concentrations. On the contrary, glucocorticoid stimulation of the transcriptional activity of the hK2 construct was the weakest among the tested steroids. The results indi cate that the steroid response elements in the proximal promoters of h PSA and hK2 genes are not androgen specific, offering the molecular ba sis for the expression of these genes outside the prostate in tissues containing steroid receptors.