Memarzadeh Sanaz, Xin Li, Mulholland David J, Mansukhani Alka, Wu Hong, Teitell Michael A, Witte Owen N
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cancer Cell. 2007 Dec;12(6):572-85. doi: 10.1016/j.ccr.2007.11.002.
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.
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。
