Heermeier K, Benedict M, Li M, Furth P, Nuñez G, Hennighausen L
Laboratory of Biochemistry and Metabolism, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1812, USA.
Mech Dev. 1996 May;56(1-2):197-207. doi: 10.1016/0925-4773(96)88032-4.
Mammary gland involution is a physiological process in which the entire organ is remodeled through the process of apoptosis. Apoptosis of secretory alveolar cells is initiated at the time of weaning, followed by the collapse and disappearance of the entire lobuloalveolar compartment. While apoptotic figures were rare in mammary epithelium of lactating mice, their number increased after weaning and reached a maximum on day 3 of involution. Active cell death continued until day 5 after weaning and only little parenchyma remained on day 8, when remodeling of the gland was completed. Bax mRNA levels increased during the first day of involution independent of the presence or absence of p53. Bax protein was detected in an increasing number of cells after weaning, peaking at day 3 and decreasing thereafter. Low levels of bcl-x mRNA and protein were present during lactation, followed by a sharp increase during the first 2 days of involution. The bcl-xS splice variant of bcl-x can promote cell death, and bcl-xL has a protective function in cell culture. The ratio of bcl-xS versus bcl-xL remained stable in the virgin, pregnant and lactating gland. However, during the first 2 days of involution, bcl-xS expression increased six-fold more than bcl-xL. To further evaluate the role of Bcl-xS which was less abundant in the mammary cells than Bcl-xL, cotransfection studies were performed in cell culture. They confirmed that Bcl-xS protein can facilitate apoptosis even when Bcl-xL is present in excess. These findings point to a significant role for Bax and Bcl-xS in the regulation of apoptosis of secretory alveolar cells during involution.
乳腺退化是一个生理过程，在此过程中整个器官通过细胞凋亡进行重塑。分泌性肺泡细胞的凋亡在断奶时开始，随后整个小叶腺泡结构塌陷并消失。在哺乳期小鼠的乳腺上皮中凋亡细胞很少见，但断奶后其数量增加，并在退化第3天达到峰值。活跃的细胞死亡一直持续到断奶后第5天，到第8天腺体重塑完成时仅残留少量实质组织。在退化的第一天，Bax mRNA水平升高，与p53的有无无关。断奶后在越来越多的细胞中检测到Bax蛋白，在第3天达到峰值，此后下降。哺乳期存在低水平的bcl-x mRNA和蛋白，在退化的前两天急剧增加。bcl-x的bcl-xS剪接变体可促进细胞死亡，而bcl-xL在细胞培养中具有保护作用。在未孕、妊娠和哺乳期腺体中，bcl-xS与bcl-xL的比例保持稳定。然而，在退化的前两天，bcl-xS的表达比bcl-xL增加了6倍。为了进一步评估在乳腺细胞中含量比Bcl-xL少的Bcl-xS的作用，在细胞培养中进行了共转染研究。这些研究证实，即使存在过量的Bcl-xL，Bcl-xS蛋白也能促进细胞凋亡。这些发现表明Bax和Bcl-xS在退化过程中分泌性肺泡细胞凋亡的调控中起重要作用。
