Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer

Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer
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DOI:
10.1158/1078-0432.ccr-0436-03
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发表时间:
2004-07-15
影响因子:
11.5
通讯作者:
Yoshida, KI
Yoshida, KI
中科院分区:
医学1区
文献类型:
--
作者:
Kamai, T;Yamanishi, T;Yoshida, KI

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Rho家族的GTP酶参与肌动蛋白细胞骨架的组织,并与人类癌症的发生和进展有关。我们研究了Rho家族GTP酶、原型RhoA、Rac 1和Cdc 42以及RhoA、ROCK-I和ROCK-II的主要下游靶标在睾丸癌中的作用。我们使用蛋白质印迹法对来自57例睾丸生殖细胞肿瘤患者手术标本的配对肿瘤和非肿瘤样本中的蛋白质表达进行定量。RhoA、ROCK-I、ROCK-II、Rac 1和Cdc 42蛋白在肿瘤组织中的表达显著高于非肿瘤组织(P < 0.0001)。RhoA、ROCK-1、ROCK-II、Rac 1和Cdc 42蛋白在高分期组的表达高于低分期组(P < 0.0001、P <0.001、P <0.0001、P < 0.0001)。在11期非恶性肿瘤(31例患者)中,与7例难治性/复发性疾病患者相比,24例治疗后无疾病证据的患者中原发肿瘤中RhoA、ROCK-I、ROCK-II、Rac 1和Cdc 42的蛋白水平较低(P < 0.05)。Rho家族GTP酶可能参与睾丸生殖细胞肿瘤的进展。
The Rho family of GTPases are involved in actin cytoskeleton organization and associated with carcinogenesis and progression of human cancers. We investigated the roles of Rho family GTPases, prototypes RhoA, Rac1, and Cdc42, and the major downstream targets of RhoA, ROCK-I, and ROCK-II in testicular cancer. We quantified protein expression in paired tumor and nontumor samples from surgical specimens from 57 consecutive patients with testicular germ cell tumors using Western blotting. Protein expression of RhoA, ROCK-I, ROCK-II, Rac1, and Cdc42 was significantly higher in tumor tissue than in nontumor tissue (P < 0.0001). Expression of protein for RhoA, ROCK-1, ROCK-II, Rac1, and Cdc42 was greater in tumors of higher stages than lower stages (P < 0.0001, P < 0.001, P < 0.001, P < 0.0001, P < 0.0001, respectively). Within stage 11 nonseminoma (31 patients), protein levels of RhoA, ROCK-I, ROCK-II, Rac1, and Cdc42 in the primary tumor were lower in the group of 24 patients with no evidence of disease after therapy compared with 7 patients with disease that was refractory/recurrent (P < 0.05). Rho family GTPases may be involved in the progression of testicular germ cell tumors.