Metz Richard P, Qu Xiaoyu, Laffin Brian, Earnest David, Porter Weston W
Department of Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843-4458, USA.
Dev Dyn. 2006 Jan;235(1):263-71. doi: 10.1002/dvdy.20605.
Mouse mammary epithelial cells (HC-11) and mammary tissues were analyzed for developmental changes in circadian clock, cellular proliferation, and differentiation marker genes. Expression of the clock genes Per1 and Bmal1 were elevated in differentiated HC-11 cells, whereas Per2 mRNA levels were higher in undifferentiated cells. This differentiation-dependent profile of clock gene expression was consistent with that observed in mouse mammary glands, as Per1 and Bmal1 mRNA levels were elevated in late pregnant and lactating mammary tissues, whereas Per2 expression was higher in proliferating virgin and early pregnant glands. In both HC-11 cells and mammary glands, elevated Per2 expression was positively correlated with c-Myc and Cyclin D1 mRNA levels, whereas Per1 and Bmal1 expression changed in conjunction with beta-casein mRNA levels. Interestingly, developmental stage had differential effects on rhythms of clock gene expression in the mammary gland. These data suggest that circadian clock genes may play a role in mouse mammary gland development and differentiation.
对小鼠乳腺上皮细胞(HC-11)和乳腺组织进行分析,以研究昼夜节律钟、细胞增殖和分化标记基因的发育变化。在分化的HC-11细胞中,生物钟基因Per1和Bmal1的表达升高,而在未分化细胞中Per2 mRNA水平更高。这种生物钟基因表达的分化依赖性模式与在小鼠乳腺中观察到的一致,因为在妊娠后期和哺乳期乳腺组织中Per1和Bmal1 mRNA水平升高,而在增殖的处女期和妊娠早期腺体中Per2表达更高。在HC-11细胞和乳腺中,Per2表达升高均与c-Myc和细胞周期蛋白D1 mRNA水平呈正相关,而Per1和Bmal1表达则与β-酪蛋白mRNA水平协同变化。有趣的是,发育阶段对乳腺中生物钟基因表达的节律有不同影响。这些数据表明,昼夜节律钟基因可能在小鼠乳腺发育和分化中起作用。