BASIC RESEARCH OF NEW GENE THERAPY FOR PROSTATE CANCER WITH GROWTH FACTOR RECEPTOR

生长因子受体前列腺癌新基因治疗的基础研究

• 批准号: 10671474
• 负责人: MATSUBARA Akio
• 金额: $ 1.79万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671474/
• 关键词: FGF; PROSTATE CANCER; GENE THERAPY; 成長因子

We have been investigating the potential roles of fibroblast growth factor receptors (FGFRs) in growth control of prostate tumors. Consequently we have recently found that hormone-dependent prostate tumor cells express FGFR2IIIb which mediates response to stromal-derived growth regulator FGF-7, while they lose the expression of FGFR2IIIb during progression from hormone-dependent to hormone-independent and escape the growth regulation by FGF-7. Instead the hormone-independent prostate tumor cells express FGFR1 and acquire autonomy. The results indicate that both restoration of FGFR2IIIb and deactivation of FGFR1 may result in a treatment of hormone-refractory prostate cancer. Thus, we induced the expression of FGFR2IIIb in hormone-independent rat prostate tumor cells by transfection. As a result, the transfected cells regained communication with stroma and not only showed reduced population growth rates, but also recovered cytokeratin expression and gland-like morphology specific to hormone-dependent tumors. We also transfected hormone-independent rat prostate tumor cells with kinase-defective FGFR1 to deactivate the endogenous FGFR1 by dominant-negative effect. As a result, in vivo growth of the transfected cells was similar to that of FGFR2IIIb-introduced cells.

我们一直在研究成纤维细胞生长因子受体（FGFR）在前列腺肿瘤生长控制中的潜在作用。因此，我们最近发现，激素依赖性前列腺肿瘤细胞表达FGFR2IIIB，它介导对基质衍生的生长调节剂FGF-7的反应，而它们失去了FGFR2IIIB的表达，从激素依赖性依赖激素依赖性和避免生长调节的过程中， FGF-7。取而代之的是激素非依赖性前列腺肿瘤细胞表达FGFR1并获得自主权。结果表明，FGFR2IIIB的恢复和FGFR1失活都可能导致治疗激素难治性前列腺癌。因此，我们通过转染诱导FGFR2IIIB在激素非依赖性大鼠前列腺肿瘤细胞中的表达。结果，转染的细胞恢复了与基质的通信，不仅显示出降低的人口生长速率，而且还恢复了细胞角蛋白表达和针对激素依赖性肿瘤的腺样形态。我们还用激酶缺陷的FGFR1转染了非激素的大鼠前列腺肿瘤细胞，以通过显性阴性效应将内源性FGFR1失活。结果，转染的细胞的体内生长与FGFR2IIIB引入的细胞的体内生长相似。

项目成果

Akio Matsubara: "Inhibition of growth of maligrant rat prostate tuno a cells by restoratron of fibroblest growth facter recetor 2" Cancer Research. 58. 1509-1514 (1998)

Akio Matsubara：“成纤维生长因子受体 2 的恢复子抑制恶性大鼠前列腺癌 a 细胞的生长”癌症研究。