IGF-2 is a mediator of prolactin-induced morphogenesis in the breast
IGF-2 is a mediator of prolactin-induced morphogenesis in the breast
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DOI：
10.1016/s1534-5807(02)00365-9
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发表时间：
2002-12-01
影响因子：
11.8
通讯作者：
Heineman, A
中科院分区：
文献类型：
--
作者：
Brisken, C;Ayyannan, A;Heineman, A
催乳素控制乳腺上皮细胞（MEC）增殖和乳腺上皮形态发生的机制尚不清楚。我们发现细胞周期蛋白 D1(-/-) MEC 无法响应催乳素而增殖，并将 IGF-2 识别为催乳素信号传导的下游靶标，位于细胞周期蛋白 D1 转录的上游。异位 IGF-2 表达可恢复催乳素受体 (-/-) 上皮细胞中的肺泡生成。 IGF-2 缺陷的 MEC 中肺泡发生延迟。 IGF-2 和催乳素受体 mRNA 共定位于乳腺上皮。在原代 MEC 中，催乳素诱导 IGF-2 mRNA，IGF-2 诱导细胞周期蛋白 D1 蛋白。因此，IGF-2 是催乳素诱导的肺泡发生的介质；催乳素、IGF-2 和细胞周期蛋白 D1 在乳腺癌中均过度表达，是乳腺发育途径的组成部分。
The mechanisms by which prolactin controls proliferation of mammary epithelial cells (MECs) and morphogenesis of the breast epithelium are poorly understood. We show that cyclin D1(-/-) MECs fail to proliferate in response to prolactin and identify IGF-2 as a downstream target of prolactin signaling that lies upstream of cyclin D1 transcription. Ectopic IGF-2 expression restores alveologenesis in prolactin receptor(-/-) epithelium. Alveologenesis is retarded in IGF-2-deficient MECs. IGF-2 and prolactin receptor mRNAs colocalize in the mammary epithelium. Prolactin induces IGF-2 mRNA and IGF-2 induces cyclin D1 protein in primary MECs. Thus, IGF-2 is a mediator of prolactin-induced alveologenesis; prolactin, IGF-2, and cyclin D1, all of which are overexpressed in breast cancers, are components of a developmental pathway in the mammary gland.