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[PAK1基因在上皮性卵巢肿瘤中过表达的意义及机制]

[Significance and mechanisms of overexpression of PAK1 gene in epithelial ovarian neoplasms].

作者信息

Xie Dan, Yang Guo-Feng, Chen Yu-Qing, Jiang Lin-Fang, Xiao Liu-Zhen

机构信息

State Key Laboratory of Oncology in Southern China, Caner Center, Sun Yat-Sen University, Guangzhou 510060, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2006 Dec;28(12):911-4.

PMID:17533742
Abstract

OBJECTIVE

To investigate the significance and mechanisms of overexpression of p21-activated kinase 1 gene (PAK1) in epithelial ovarian neoplasms.

METHODS

Immunohistochemistry, fluorescence in situ hybridization and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling methods were used to examine the protein expression and amplification of PAK1 and cell apoptosis in 30 benign ovarian adenomas, 20 borderline tumors and 80 ovarian carcinomas by tissue microarray.

RESULTS

In immunohistochemistry study, overexpression of PAK1 protein was observed in 7 (25.9%) informative benign ovarian adenomas, 7 (36.8%) borderline tumors and 53 (68.8%) ovarian carcinomas. A significant inverse correlation of PAK1 overexpression and cell apoptosis was observed in these epithelial ovarian neoplasm cohorts (P = 0.002). In addition, 27/31 (87.1%) poorly differentiated (G3) carcinomas showed overexpression of PAK1, the frequency was significantly higher than that in tumors of G1 - G2 (26/46, 56.5% , P =0.01). In fluorescence in situ hybridization study, only 2 (4.7%) informative ovarian carcinomas showed amplification of PAK1 gene. None of the borderline and benign ovarian tumors showed PAK1 amplification.

CONCLUSION

Overexpression of PAK1 protein may be involved in the tumorigenesis of epithelial ovarian neoplasms and it is associated closely with the malignant histological phenotype of ovarian carcinomas. Mechanism other than gene amplification of PAK1 may play a more important role in the regulation of protein expression of PAK1 in ovarian tumors.

摘要

目的

探讨p21激活激酶1基因(PAK1)在上皮性卵巢肿瘤中过表达的意义及机制。

方法

采用免疫组织化学、荧光原位杂交及末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法,通过组织芯片检测30例良性卵巢腺瘤、20例交界性肿瘤和80例卵巢癌中PAK1的蛋白表达、扩增情况及细胞凋亡。

结果

免疫组织化学研究显示,在可评估的良性卵巢腺瘤中7例(25.9%)、交界性肿瘤中7例(36.8%)、卵巢癌中53例(68.8%)观察到PAK1蛋白过表达。在这些上皮性卵巢肿瘤队列中观察到PAK1过表达与细胞凋亡呈显著负相关(P = 0.002)。此外,27/31例(87.1%)低分化(G3)癌显示PAK1过表达,其频率显著高于G1 - G2级肿瘤(26/46,56.5%,P = 0.01)。荧光原位杂交研究显示,仅2例(4.7%)可评估的卵巢癌显示PAK1基因扩增。交界性和良性卵巢肿瘤均未显示PAK1扩增。

结论

PAK1蛋白过表达可能参与上皮性卵巢肿瘤的发生,且与卵巢癌的恶性组织学表型密切相关。PAK1基因扩增以外的机制可能在卵巢肿瘤PAK1蛋白表达调控中起更重要作用。

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