The study of roles of Rho family GTPase in progression and metastasis of renal cell cancer

Rho家族GTPase在肾细胞癌进展和转移中的作用研究

• 批准号: 14571517
• 负责人: KAMAI Takao
• 金额: $ 2.11万
• 依托单位: Dokkyo University School of Medicine (32203)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571517/
• 关键词: Rho; GTPase; ROCK; Renal cell carcinoma; Invasion; Metastasis; Recurrence; Prognosis; 腎; 癌; Rac; Cdc42; 腎細胞癌

We analyzed the mRNA levels of RhoA, RhoB, RhoC and ROCK gene in the surgical specimens of RCC tissues from 78 consecutive Japanese patients and in the corresponding non-tumor tissue originating from the same patient using polymerase chain reaction after reverse transcription (RT-PCR). We compared their expression levels in tumor tissues with those in non-tumor tissues and evaluated the relationship between their expression levels in tumors and clinicopathological features.The mRNA levels of RhoC and ROCK were increased in tumor tissues, compared with those in non-tumor tissues of the resected testis (P<0.0001, P<0.0001, respectively). There was no difference between the expression levels of mRNAs for RhoA. Although RhoB mRNA levels were higher in tumor tissues than those in non-tumor tissues (P<0.05), its expression was not associated with tumor grade, stage and prognosis. The increase of the RhoC and ROCK mRNA levels was related to the tumor grade (P<0.05, P<0.05, respectively) and s … More tage (P<0.0001, P<0.0001, respectively). There was a positive relationship between expression levels of mRNAs of RhoC and ROCK in tumor tissues (P<0.0001). Kaplan-Meier plots of survival rate in patients with low versus high mRNA levels of RhoC and ROCK showed that high mRNA levels of RhoC and ROCK were associated with overall survival (P<0.0001, P<0.0001, respectively). Multivariate analysis showed that mRNA levels of RhoC and ROCK were independent prognostic factors in overall survival.In renal pelvis and ureter cancer, the higher expression of RhoA and ROCK proteins were associated poorly differentiated grade, higher stage, and unfavorable prognosis 1).In bladder cancer, although the higher protein levels of RhoA, RhoC, and ROCK were related to poorly differentiated grade, higher stage, and unfavorable prognosis, the lower RhoB levels were shown in advanced tumors 2).In testicular germ cell tumor, the higher expressions of RhoA, ROCK, Rac1 and Cdc42 were associated with advanced stage of the disease 3). Less

采用逆转录后聚合酶链式反应(RT-PCR)技术检测78例日本肾癌手术标本和相应的非肿瘤组织中RhoA、RhoB、RhoC和ROCK基因的表达水平。我们比较了它们在肿瘤组织和非肿瘤组织中的表达水平，并探讨了它们在肿瘤组织中的表达水平与临床病理特征的关系。与切除的非肿瘤组织相比，肿瘤组织中RhoC和ROCK的基因表达水平升高(分别为P&lt；0.0001，P&lt；0.0001)。RhoA的mRNAs表达水平无明显差异。虽然RhoB在肿瘤组织中的表达水平高于非肿瘤组织(P&lt；0.05)，但其表达与肿瘤的分级、分期及预后无关。RhoC和ROCK基因表达水平的升高与肿瘤分级(P<0.05)和S…有关更多的Tage(分别为P&lt；0.0001和P&lt；0.0001)。肿瘤组织中RhoC和ROCK的mRNAs表达水平呈正相关(P&lt；0.0001)。在Rhoc和ROCK基因表达水平低和高表达的患者中，生存率的Kaplan-Meier曲线图显示，RhoC和ROCK基因表达水平高与总生存期相关(P&lt；0.0001，P&lt；0.0001)。多因素分析显示，RhoA、RhoC和ROCK的表达水平是影响患者总体生存的独立预后因素，RhoA和ROCK蛋白的高表达与肾癌的低分化程度、高分期和不良预后相关1)。在膀胱癌中，虽然RhoA、RhoC和ROCK的高蛋白表达与低分化程度、高分期和不良预后有关，但在晚期肿瘤中RhoB的表达水平较低。较少

项目成果

Takao Kamai, Satoru Kawakami, Fumitaka Koga, Gaku Arai, Kentaro Takagi, Kyoko Arai, Toshihiko Tsujii, Ken-ichiro Yoshida: "RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer."BJU Int.. 89. 449-453 (2003)

Takao Kamai、Satoru Kawakami、Fumitaka Koga、Gaku Arai、Kentaro Takagi、Kyoko Arai、Toshihiko Tsujii、Ken-ichiro Yoshida：“RhoA 与上尿路癌的侵袭和淋巴结转移有关。”BJU Int.. 89. 449

Takao Kamai: "Significant association of Rho/ROCK Pathway with invasion and metastasis of bladder cancer."Clin.Cancer Res.. 9(7). 2632-2641 (2003)

Takao Kamai：“Rho/ROCK 通路与膀胱癌侵袭和转移的显着关联。”Clin.Cancer Res.. 9(7)。

Takao Kamai: "The rho/rho-kinase pathway is involved in the progression of testicular germ cell tumour"BJU International. 89. 449-458 (2002)

Takao Kamai：“rho/rho-激酶途径参与睾丸生殖细胞肿瘤的进展”BJU International。

Takao Kamai, Tomonori Yamanishi, Hiromichi Shirataki, Kentaro Takagi, Hidekazu Asami, Yuji Ito, Ken-Ichiro Yoshida.: "Overexpression of RhA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer."Clin Cancer Res.. (acceptance). (2004

Takao Kamai、Tomonori Yamanishi、Hiromichi Shirataki、Kentaro Takagi、Hidekazu Asami、Yuji Ito、Ken-Ichiro Yoshida.：“RhA、Rac1 和 Cdc42 GTP 酶的过度表达与睾丸癌的进展相关。”Clin Cancer Res..（接受

Takao Kamai: "RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer"BJU International. 9. 234-238 (2003)

Takao Kamai：“RhoA 与上尿路癌的侵袭和淋巴结转移有关”BJU International。