Regulation of the expression of protein kinase C isoenzymes in rat ventral prostate: effects of age, castration and flutamide treatment.
Protein kinase C (PKC) isoenzymes are involved in cell function, growth, apoptosis and neoplastic transformation in the prostate gland. We detected by means of Western blot the expression of the classical alpha and beta1, the novel epsilon and the atypical zeta isoforms of PKC in ventral prostates from rats with different extents of plasma testosterone levels and/or androgen imprinting on the gland. The expression of the four isoforms decreased in 5-day castrated rats showing apoptotical regression of the gland and a drastic reduction of circulating testosterone. However, the expression of PKC isoenzymes (alpha, beta1, epsilon ) increased in prostates from pubertal (35-days old) rats that are characterized by relatively low but extremely bioactive testosterone plasma levels. Treatment of adult rats for 14 days with flutamide (daily s.c. injection of 15 mg/Kg B.W.) resulted in increased expression of the four isoenzymes; it occurred in the presence of increased (normal rats) or drastically reduced (rats castrated after 9 days of flutamide administration) levels of plasma testosterone conceivably through a direct effect of this nonsteroidal antiandrogen on prostate cells. Measurements of PKC(alpha) activity were in agreement with the observations on protein expression and showed that flutamide (that is extensively used in the treatment of advanced prostate cancer) elicits some impairment in the mechanisms of translocation of this isoform from the cytosol to the membrane. Thus, in addition to the possibility of direct effects of flutamide upon the rat prostate, we present evidence that the levels of circulating androgens and/or their bioactivity in the gland regulate the expression of various important PKC isoforms.
Montalvo
Leire
L
Department of Biochemistry and Molecular Biology, University of Alcalá, E-28871 Alcalá de Henares, Spain.
Sánchez-Chapado
Manuel
M
Prieto
Juan C
JC
Carmena
María J
MJ
D000375:Aging; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D005485:Flutamide / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects* / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood
D000726:Androgen Antagonists; D007527:Isoenzymes; D013739:Testosterone; D005485:Flutamide; D011493:Protein Kinase C