增强的旁分泌成纤维细胞生长因子10（FGF10）表达促进多灶性前列腺腺癌的形成以及上皮雄激素受体的增加。
Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor.
作者信息
Memarzadeh Sanaz, Xin Li, Mulholland David J, Mansukhani Alka, Wu Hong, Teitell Michael A, Witte Owen N
机构信息
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
出版信息
Cancer Cell. 2007 Dec;12(6):572-85. doi: 10.1016/j.ccr.2007.11.002.
Abstract
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 FGF10-induced carcinoma was serially transplantable. Paracrine FGF10 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 FGF10/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.
摘要
FGF10间充质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。使用显性负性FGFR1（DN FGFR1）抑制上皮FGFR1信号传导可导致癌症表型逆转。FGF10诱导的癌的一个亚群可连续移植。旁分泌FGF10导致上皮雄激素受体增加，并与细胞自主激活的AKT协同作用。我们的观察结果表明，基质FGF10表达可能促进前列腺腺癌中观察到的多灶性组织学变化，并提示FGF10/FGFR1轴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启动致癌转化。
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