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.