FGFR2 gene mutation in human prostate cancer : Close relation to loss of hormone dependency and therapeutic application

成纤维细胞生长因子（FGF）及其受体（FGFR）在人前列腺的发育和稳态中促进基质-上皮通讯。响应于基质FGF 7和FGF 10的驻留上皮细胞FGFR2IIIb的丧失伴随模型动物和人前列腺肿瘤的恶性进展。我们研究了通过在恶性人前列腺肿瘤PC-3细胞系中转染FGFR2IIIb是否恢复了与恶性程度较低的肿瘤相关的细胞特性。通过转染在PC-3细胞中表达FGFR2IIIb导致体外生长抑制和体内肿瘤形成减少，同时增加细胞分化和凋亡。此外，我们研究了辐射与FGFR2IIIb在PC-3细胞中的协同作用。辐射显着减少转染PC-3细胞的集落数。结果表明，FGFR 2IIIb对恶性人前列腺上皮细胞原型PC-3的恢复恢复了与非恶性肿瘤和正常细胞相关的性质。这进一步表明，上皮细胞驻留，促进稳态的FGFR 2可能参与抑制恶性肿瘤和恢复可能是一个候选的基因治疗的前列腺癌的肿瘤难治性。

Fibroblast growth factors (FGFs) and their receptors (FGFRs) expedite stromal-epithelial communication in development and homeostasis of the human prostate. Loss of resident epithelial cell FGFR2IIIb that responds to stromal FGF7 and FGF10 accompanies malignant progression of both model animal and human prostate tumors. We examined whether restoration of FGFR2IIIb by transfection in the malignant human prostate tumor PC-3 cell line restored cellular properties associated with less malignant tumors. Expression of FGFR2IIIb in PC-3 cells by transfection resulted in growth suppression in vitro and reduced tumor formation in vivo concurrent with increased cellular differentiation and apoptosis. Furthermore, we investigated the synergistic effects of radiation with the FGFR2IIIb in PC-3 cells. Radiation dramatically decreased the number of colonies in transfected PC-3 cells. The results indicate that restoration of FGFR2IIIb to the malignant human prostate epithelial cell prototype PC-3 restores properties associated with nonmalignant tumors and normal cells. This further suggests that epithelial cell resident, homeostasis-promoting FGFR2 may be involved in suppression of malignancy and that restoration may be a candidate for gene therapy of hormone-refractory prostate cancer.