Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor
Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor
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DOI：
10.1016/j.ccr.2007.11.002
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发表时间：
2007-12-01
期刊：
影响因子：
50.3
通讯作者：
Witte, Owen N.
中科院分区：
文献类型：
--
作者：
Memarzadeh, Sanaz;Xin, Li;Witte, Owen N.
成纤维细胞生长因子10（FGF10）在间质中表达增强导致多灶性前列腺上皮内瘤变（PIN）或前列腺癌的形成。使用显性失活的成纤维细胞生长因子受体1（DN FGFR1）抑制上皮细胞的FGFR1信号传导可导致癌症表型逆转。由FGF10诱导的一部分癌可以连续移植。旁分泌的FGF10导致上皮雄激素受体增加，并与细胞自主性激活的蛋白激酶B（AKT）协同作用。我们的观察结果表明，间质中FGF10的表达可能促进在前列腺腺癌中观察到的多灶性组织学特征，并提示FGF10/FGFR1轴可作为治疗激素敏感性或难治性前列腺癌的潜在治疗靶点。我们还表明，短暂暴露于旁分泌生长因子可能足以引发致癌转化。
Enhanced mesenchymal expression of FGF10 led to the formation of multifocal PIN or prostate cancer. Inhibition of epithelial FGFR1 signaling using DN FGFR1 led to reversal of the cancer phenotype. A subset of the FGH10-induced carcinoma was serially transplantable. Paracrine FGH10 led to an increase in epithelial androgen receptor and synergized with cell-autonomous activated AKT. Our observations indicate that stromal FGF10 expression may facilitate the multifocal histology observed in prostate adenocarcinoma and suggest the FGH10/FGFR1 axis as a potential therapeutic target in treating hormone-sensitive or refractory prostate cancer. We also show that transient exposure to a paracrine growth factor may be sufficient for the initiation of oncogenic transformation.