Socs2 and Elf5 mediate prolactin-induced mammary gland development
Socs2 and Elf5 mediate prolactin-induced mammary gland development
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DOI：
10.1210/me.2005-0473
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发表时间：
2006-05-01
影响因子：
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通讯作者：
Ormandy, CJ
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文献类型：
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作者：
Harris, J;Stanford, PM;Ormandy, CJ
乳腺腺泡形态发生的增殖期在妊娠早期通过血清催乳素和孕酮水平的升高而启动，建立了最终负责小叶腺泡发育和泌乳开始的基因表达程序。为了探索这在很大程度上是未知的遗传程序，我们构建了来自移植的乳腺泌乳素受体（Prlr）基因敲除或野生型乳腺上皮细胞与野生型乳腺基质重组形成的转录谱。与来自催乳素处理的Scp2乳腺上皮细胞的配置文件的比较产生了一小部分通常催乳素调节的基因，包括细胞因子信号传导的负调节因子Socs2（细胞因子信号传导抑制因子2）和ets转录因子E74样因子5（Elf5）。Socs2的纯合无效突变挽救了泌乳失败和乳腺信号转导子和转录激活子5磷酸化的减少，这是Prlr杂合子小鼠的特征，表明乳腺Socs2是催乳素信号通路的关键调节因子。Elf5在Prlr缺失型乳腺上皮中的再表达恢复了小叶肺泡发育和产奶，表明Elf5是一种能够取代催乳素信号传导的转录因子。因此，Socs2和Elf5是一组催乳素调节基因的关键成员，这些基因介导催乳素驱动的乳腺发育。
The proliferative phase of mammary alveolar morphogenesis is initiated during early pregnancy by rising levels of serum prolactin and progesterone, establishing a program of gene expression that is ultimately responsible for the development of the lobuloalveoli and the onset of lactation. To explore this largely unknown genetic program, we constructed transcript profiles derived from transplanted mammary glands formed by recombination of prolactin receptor (Prlr) knockout or wildtype mammary epithelium with wild-type mammary stroma. Comparison with profiles derived from prolactin-treated Scp2 mammary epithelial cells produced a small set of commonly prolactin-regulated genes that included the negative regulator of cytokine signaling, Socs2 (suppressor of cytokine signaling 2), and the ets transcription factor, E74-like factor 5 (Elf5). Homozygous null mutation of Socs2 rescued the failure of lactation and reduction of mammary signal transducer and activator of transcription 5 phosphorylation that characterizes Prlr heterozygous mice, demonstrating that mammary Socs2 is a key regulator of the prolactin-signaling pathway. Reexpression of Elf5 in Prlr nullizygous mammary epithelium restored lobuloalveolar development and milk production, demonstrating that Elf5 is a transcription factor capable of substituting for prolactin signaling. Thus, Socs2 and Elf5 are key members of the set of prolactin-regulated genes that mediate prolactin-driven mammary development.