Masso-Welch P A, Verstovsek G, Ip M M
Department of Pharmacology and Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Eur J Cell Biol. 1999 Jul;78(7):497-510. doi: 10.1016/s0171-9335(99)80076-4.
Protein kinase C (PKC) is involved in signaling 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 PKCs 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, PKCs 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 in the nucleus, and PKC zeta was concentrated in the subapical region of the luminal epithelium. Additionally, marked staining for PKCs 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 PKCs 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 (PKCs epsilon and zeta) or more intensely (PKCs 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 by alterations in signaling in the alveolar myoepithelium.
蛋白激酶C（PKC）参与调节多种细胞类型（包括乳腺上皮细胞）增殖和分化的信号传导过程。此外，在乳腺癌发生过程中已观察到PKC表达或活性的变化。为了研究特定PKC亚型在正常乳腺发育过程中的作用，我们检测了青春期、孕期、哺乳期和退化期PKCα、δ、ε和ζ的表达及定位。通过免疫印迹分析，在从青春期到孕期的转变过程中，乳腺上皮类器官中PKCα、δ、ε和ζ蛋白的表达增加。在乳腺冰冻切片中，PKCα、δ、ε和ζ在管腔上皮和肌上皮中染色，在不同亚型和发育阶段有特定的定位。孕期管腔上皮中PKCα呈点状顶端定位。哺乳期，PKCε存在于细胞核中，PKCζ集中在管腔上皮的顶端下区域。此外，在导管和腺泡底部的肌上皮细胞中观察到PKCα、δ、ε和ζ有明显染色。这种基底导管和腺泡染色在发育上有特定的强度差异。在大多数时间点（处女期、孕期、哺乳期和早期退化期），导管的肌上皮细胞比腺泡内衬的肌上皮细胞对PKCα、δ、ε和ζ的染色更强。在退化后期（第9 - 12天），导管的优先染色消失或逆转，退化腺泡结构内衬的肌上皮细胞对PKCε和ζ染色相同，对PKCα和δ染色更强，这与退化腺泡周围肌上皮细胞增厚一致。退化期腺泡底部PKC亚型染色增加表明腺泡退化可能受腺泡肌上皮信号改变的影响。
