Protein kinase C pathway potentiates androgen-mediated gene expression of the mouse vas deferens specific aldose reductase-like protein (MVDP).
Transcription of the mouse vas deferens protein (MVDP) gene, a member of the aldo-keto reductase superfamily, is stimulated by androgens via the androgen responsive element (ARE) located in the proximal promoter (-111 to -97). We investigated interaction between androgens and the protein kinase C (PKC) signalling pathway. Transcriptional regulation was determined by analysis of chloramphenicol acetyltransferase (CAT). T47D cells were transiently transfected with 5' flanking MVDP DNA promoter sequences (-1804 to +41; -510 to +41 and -121 to +41) fused to the reporter (CAT) gene. Androgen-induced transcriptional activity can be enhanced from 6 (1.8 and 0.5 kb MVDP-CAT constructs) to 18 fold (0.16 kb MVDP-CAT construct), in a time and dose-dependent manner, by the PKC activator 12-o-tetradecanoylphorbol-13 acetate (TPA). A mutation in the proximal ARE abolished both androgen and TPA-dependent gene enhancement. TPA influenced minimally MMTV promoter in T47D cells and MVDP promoter in CV1 cells suggesting that the effects of the PKC activator are probably promoter and cell-specific. In contrast, activation of protein kinase A (PKA) via addition of dibutyryl-cAMP (db-cAMP) reduced androgen induction of the MVDP gene.
Fabre
S
S
Laboratoire de Physiologie Comparée et Endocrinologie, CNRS URA 1940, Université Blaise Pascal-Clermont Ferrand II, Aubière, France.
Darne
C
C
Veyssière
G
G
Jean
C
C
D000449:Aldehyde Reductase; D000818:Animals; D001943:Breast Neoplasms; D003994:Bucladesine / Q000494:pharmacology; D002277:Carcinoma; D002460:Cell Line; D002522:Chlorocebus aethiops; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000502:physiology*; D011506:Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014649:Vas Deferens / Q000502:physiology*
D011506:Proteins; D011993:Recombinant Fusion Proteins; D013196:Dihydrotestosterone; D003994:Bucladesine; C066498:Akr1b7 protein, mouse; D000449:Aldehyde Reductase; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate