Alterations in the expression and localization of protein kinase C isoforms during mammary gland differentiation

摘要

Protein kinase C (PKC) is involved in signalling that modulates the proliferation and differentiation of many cell types, including mammary epithelial cells. In addition, changes in PKC expression or activity have been observed during mammary carcinogenesis. In order to examine the involvement of specific PKC isoforms during normal mammary gland development, the expression and localization of PKC alpha, delta, epsilon and zeta were examined during puberty, pregnancy, lactation and involution. By immunoblot analysis, expression of PKC alpha, delta, epsilon and zeta proteins was increased in mammary epithelial organoids during the transition from puberty to pregnancy. In mammary gland frozen sections, PKC alpha, delta, epsilon and zeta were stained in the luminal epithelium and myoepithelium, in varying isoform- and developmental stage-specific locations. PKC alpha was found in a punctate apical localization in the luminal epithelium during pregnancy. During lactation, PKC epsilon was present inthe nucleus, and PKC zeta was concentrated in the subapical region of the luminal epithelium. Additionally, marked staining for PKC alpha, delta, epsilon and zeta was observed in the myoepithelial cells at the base of ducts and alveoli. This basal ductal and alveolar staining differed in intensity in a developmentally-specific fashion. During most time points (virgin, pregnant, lactating and early involution), myoepithelial cells of the duct were more intensely stained than those lining the alveoli for PKC alpha, delta, epsilon and zeta, During late involution (days 9-12), the preferential staining of ducts was lost or reversed, and the myoepithelial cells lining the regressing alveolar structures stained equally (PKC epsilon and zeta) or more intensely (PKC alpha and delta), coincident with the thickening of the myoepithelial cells surrounding the regressing alveoli. The increased PKC isoform staining at the base of alveoli during involution suggests that alveolar regression may be influenced byalterations in signalling in the alveolar myoepithelium.