Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic morphogenesis and the acquisition of strict androgen dependency for adult tissue homeostasis
Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic morphogenesis and the acquisition of strict androgen dependency for adult tissue homeostasis
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DOI：
10.1242/dev.02765
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发表时间：
2007-02-15
期刊：
影响因子：
4.6
通讯作者：
Wang, Fen
中科院分区：
文献类型：
--
作者：
Lin, Yongshun;Liu, Guoqin;Wang, Fen
成纤维细胞生长因子（FGF）家族由22个成员组成，并通过激活FGF受体酪氨酸激酶（FGFR）的不同同种型来调节广谱生物活性。在FGF中，FGF 7和FGF 10通过经由FGFR 2同种型的信号传导参与前列腺发育和前列腺组织稳态的调节。在小鼠中使用Cre-LoxP系统的条件性基因消融，我们证明了泌尿生殖上皮细胞-前列腺上皮细胞的前体-前列腺分支形态发生和前列腺生长对FGFR 2的组织特异性要求。大多数Fgfr 2条件无效（Fgfr 2（cn））胚胎仅发育两个背侧前列腺（dp）和两个侧前列腺（lp）叶。这与野生型前列腺形成对比，野生型前列腺有两个前列腺前叶（ap），两个dp，两个lp和两个前列腺腹叶（vp）。与由发育良好的上皮导管网络组成的野生型前列腺不同，Fgfr 2（cn）前列腺尽管保留了分隔的组织结构，但表现出原始的上皮结构。此外，虽然Fgfr 2（CN）前列腺继续产生分泌蛋白的雄激素依赖性的方式，他们对雄激素的组织稳态反应不佳。结果表明，FGFR 2是重要的前列腺器官发生和前列腺发育成一个严格的雄激素依赖性器官的组织稳态，但不分泌功能，这意味着雄激素可能调节组织稳态和组织功能不同。因此，Fgfr 2（cn）前列腺提供了一个有用的动物模型，仔细研究雄激素调节前列腺生长，稳态和功能的分子机制，并可能产生关于晚期肿瘤前列腺细胞如何逃避严格的雄激素调节的线索。
The fibroblast growth factor (FGF) family consists of 22 members and regulates a broad spectrum of biological activities by activating diverse isotypes of FGF receptor tyrosine kinases (FGFRs). Among the FGFs, FGF7 and FGF10 have been implicated in the regulation of prostate development and prostate tissue homeostasis by signaling through the FGFR2 isoform. Using conditional gene ablation with the Cre-LoxP system in mice, we demonstrate a tissue-specific requirement for FGFR2 in urogenital epithelial cells -the precursors of prostatic epithelial cells -for prostatic branching morphogenesis and prostatic growth. Most Fgfr2 conditional null (Fgfr2(cn)) embryos developed only two dorsal prostatic (dp) and two lateral prostatic (lp) lobes. This contrasts to wild-type prostate, which has two anterior prostatic (ap), two dp, two lp and two ventral prostatic (vp) lobes. Unlike wild-type prostates, which are composed of well developed epithelial ductal networks, the Fgfr2(cn) prostates, despite retaining a compartmented tissue structure, exhibited a primitive epithelial architecture. Moreover, although Fgfr2(cn) prostates continued to produce secretory proteins in an androgen-dependent manner, they responded poorly to androgen with respect to tissue homeostasis. The results demonstrate that FGFR2 is important for prostate organogenesis and for the prostate to develop into a strictly androgen-dependent organ with respect to tissue homeostasis but not to the secretory function, implying that androgens may regulate tissue homeostasis and tissue function differently. Therefore, Fgfr2(cn) prostates provide a useful animal model for scrutinizing molecular mechanisms by which androgens regulate prostate growth, homeostasis and function, and may yield clues as to how advanced-tumor prostate cells escape strict androgen regulations.