Involvement of protein kinase C in mouse mammary gland development.
The relationship between kinase C activity and mammary gland differentiation was investigated by following kinase activity throughout the mouse reproductive cycle and by pharmacologically perturbing the kinase, while monitoring biochemical differentiation. Protein kinase C activity declined during pregnancy and remained low throughout lactation, suggesting an inverse relationship with milk protein expression. This negative association was further supported by the use of quercetin (50-100 mumol/l) and gossypol (50 mumol/l), which are both protein kinase C inhibitors. These compounds doubled alpha-lactalbumin levels in mammary explants cultured with hormones. However, a phorbol ester, known to activate protein kinase C, had no effect on alpha-lactalbumin production, although it did stimulate this milk protein 2.5-fold in the presence of the calcium ionophore, A23187. In the absence of raised calcium levels, protein kinase C activity therefore appeared to be inversely correlated with biochemical differentiation; but, in the presence of increased calcium concentrations, both calcium and the kinase acted synergistically to augment hormone-induced alpha-lactalbumin expression.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D005260:Female; D006072:Gossypol / Q000494:pharmacology; D007768:Lactalbumin / Q000378:metabolism; D007774:Lactation; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011270:Pregnancy, Animal; D011493:Protein Kinase C / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology
D000001:Calcimycin; D007768:Lactalbumin; D011794:Quercetin; D011493:Protein Kinase C; D006072:Gossypol