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Hormonal Regulation of Prostate-specific Antigen Messenger RNA in Human Prostatic Adenocarcinoma Cell Line LNCaP¹

Departments of Urology [C. Y-F Y., B. T. M., P. E. A., S. Q., D. L. B., D. J. T.] and Biochemistry and Molecular Biology [D. J. T.], Mayo Clinic/Foundation, Rochester, Minnesota 55905

Prostate-specific antigen (PSA) is a member of the kallikrein gene family and is expressed exclusively in human prostatic epithelial cells. PSA protein has been an important biological marker for prostate cancers. Until now, very little was known about the regulation of PSA expression in prostatic cells. In this study, we have developed a specific oligonucleotide probe which recognizes PSA but not the human glandular kallikrein. This is crucial because both PSA and human glandular kallikrein are expressed in the prostate at relatively high levels and have high nucleotide sequence homology (>82%). Utilizing a ³⁵S-labeled PSA-specific probe, PSA mRNA was localized within the glandular epithelium of the prostate. Northern blot analysis detected a single 1.6-kilobase transcript in LNCaP cells, a cell line derived from a human prostate adenocarcinoma metastasis. Therefore, LNCaP cells were used to study the androgenic effects on PSA mRNA expression. A time course study demonstrated that PSA mRNA was induced by mibolerone (a nonmetabolizable synthetic androgen) and reached maximal levels after 9 h. The induction of PSA mRNA required as little as 0.3 nM mibolerone. In addition to mibolerone, PSA mRNA could be induced by the natural androgen, dihydrotestosterone, but not by the synthetic glucocorticoid, dexamethasone, or the synthetic estrogen, diethylstilbestrol. Moreover, in the presence of dihydrotestosterone, PSA mRNA was depressed by hydroxyflutamide (an antiandrogen). These results suggest strongly that the androgenic effects on PSA mRNA in LNCaP cells may be via the function of the androgen receptor.

¹ This work was supported in part by Mayo Eagles Cancer Research Fund 102 and NIH Grant CA32387.

² To whom requests for reprints should be addressed, at Department of Urology, Guggenheim 17, Mayo Clinic, Rochester, MN.

Received 3/25/91. Accepted 5/ 6/91.

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