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

人类前列腺癌中的FGFR2基因突变：与激素依赖性丧失和治疗应用密切相关

• 批准号: 15591690
• 负责人: MATSUBARA Akio
• 金额: $ 2.24万
• 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: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591690/
• 关键词: Fibroblast growth factor; Fibroblast growth factor receptor; Tyrosine kinase; Growth inhibition; Differentiation; Prostate cancer; Radiation; Gene therapy; ヒト前立腺癌; FGFR2; アポトーシス; FRS2; MAP Kinase; 遺伝子変異; MAP kinase

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.

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FGFR 2 IIIb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FGFR 2 IIIb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FGFR 2 IIIb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FGFR 2 IIIb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 2 IIIb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。

项目成果

IGFBP-rP1の発現回復によるヒト前立腺癌細胞の放射線感受性

通过恢复 IGFBP-rP1 表达来提高人前列腺癌细胞的放射敏感性

• 发表时间: 2004
• 期刊: 日本泌尿器科学会雑誌 95
• 作者: Kubo;N.;Hiroaki Yasumoto;Mituhiro Seki;望月英樹;石 光弘
• 通讯作者: 石 光弘

線維芽細胞成長因子受容体2の発現回復によるヒト前立腺癌細胞の放射線感受性

通过恢复成纤维细胞生长因子受体2表达来提高人前列腺癌细胞的放射敏感性

• 发表时间: 2004
• 期刊: 日本泌尿器科学会雑誌 95
• 作者: Kubo;N.;Hiroaki Yasumoto;Mituhiro Seki;望月英樹
• 通讯作者: 望月英樹

Restration of fibroblast growth factor receptor 2 increases radiosensitivity of human prostate cancer.

成纤维细胞生长因子受体 2 的重新抑制会增加人类前列腺癌的放射敏感性。

• 发表时间: 2004
• 期刊: Jpn J Urol 95
• 作者: Inoue K;Chikazawa M;Fukata S;Yoshikawa C;Shuin T.;Nishimura K et al.;Nishimura Kazuo;Nishimura K;Nishimura K et al.;Inoue Hitoshi;Inoue H et al.;Inoue Hitoshi;西村和郎;Nishimura Kazuo;Hiroaki Yasumoto;Hideki Mochizuki;Hideki Mochizuki;Mitsuhiro Seki;望月英樹;石 光弘;Hiroaki Yasumoto;Hideki Mochizuki;Hideki Mochizuki;Mitsuhiro Seki;Mochizuki Hideki
• 通讯作者: Mochizuki Hideki

Restration of IGFBP-γ p1 increases radiosensitivity in hormone-refractory human prostate cancer.

重新抑制 IGFBP-γ p1 会增加激素难治性人类前列腺癌的放射敏感性。

• 发表时间: 2004
• 期刊: BJU Int. 94 Supple.2
• 作者: Inoue K;Chikazawa M;Fukata S;Yoshikawa C;Shuin T.;Nishimura K et al.;Nishimura Kazuo;Nishimura K;Nishimura K et al.;Inoue Hitoshi;Inoue H et al.;Inoue Hitoshi;西村和郎;Nishimura Kazuo;Hiroaki Yasumoto;Hideki Mochizuki;Hideki Mochizuki;Mitsuhiro Seki;望月英樹;石 光弘;Hiroaki Yasumoto;Hideki Mochizuki;Hideki Mochizuki;Mitsuhiro Seki;Mochizuki Hideki;Mitsuhiro Seki;Mochizuki Hideki;Seki Mitsuhiro
• 通讯作者: Seki Mitsuhiro

Interaction of ligant-receptor system between stromal-cell-derived factor-1 and CXC chemokine receptor 4 in human prostate cancer : a possible predictor of metastasis.

人前列腺癌中基质细胞衍生因子 1 和 CXC 趋化因子受体 4 之间配体受体系统的相互作用：可能的转移预测因子。

• 发表时间: 2004
• 期刊: Biochem Biophys Res Commun 320・3
• 作者: Inoue K;Chikazawa M;Fukata S;Yoshikawa C;Shuin T.;Nishimura K et al.;Nishimura Kazuo;Nishimura K;Nishimura K et al.;Inoue Hitoshi;Inoue H et al.;Inoue Hitoshi;西村和郎;Nishimura Kazuo;Hiroaki Yasumoto;Hideki Mochizuki;Hideki Mochizuki;Mitsuhiro Seki;望月英樹;石 光弘;Hiroaki Yasumoto;Hideki Mochizuki;Hideki Mochizuki;Mitsuhiro Seki;Mochizuki Hideki;Mitsuhiro Seki;Mochizuki Hideki;Seki Mitsuhiro;Mochizuki Hideki
• 通讯作者: Mochizuki Hideki