Zheng Xiang-Yi, Ding Wei, Xie Li-Ping, Chen Zhao-Dian
Department of Urology, First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, PR China.
Ai Zheng. 2004 Feb;23(2):215-8.
BACKGROUND & OBJECTIVE: The F-box protein Skp2 is required for the ubiquitin-mediated proteolysis of the cyclin-depended kinase inhibitor p27(kip1). Overexpression of Skp2 has been reported in many cancers, including breast carcinoma, gastric carcinoma, and prostate cancer. The purpose of this study was to investigate the correlation of Skp2 and p27(kip1) expression with the clinicopathological features of prostatic carcinoma, and the correlation between expression of Skp2 and p27(kip1) in prostate cancer.
Skp2 and p27(kip1) protein expression were evaluated in the tissues of 41 human prostatic carcinomas as well as 20 benign prostatic hyperplasia (BPH) using immunohistochemistry (EnVision method).
The Skp2 labeling frequency in prostatic carcinoma (8.52%+/-2.40%) was significantly higher than that in BPH (0.21%+/-0.15%)(P< 0.001). The Skp2 protein expression in prostatic carcinoma was positively correlated with preoperative serum prostate-specific antigen level (r=0.360,P=0.021), extraprostatic extension (r=0.570,P< 0.001), tumor stage (r=0.531, P< 0.001), and histological grade (r=0.514,P=0.001). The p27(kip1) labeling frequency in prostatic carcinoma(70.71%+/-4.25%) was significantly lower than that in BPH (97.21%+/-2.10%) (P< 0.001). The p27(kip1) protein expression in prostatic carcinoma was inversely correlated with preoperative serum prostate-specific antigen level (r=-0.399,P=0.010), extraprostatic extension (r=-0.329, P=0.036), tumor stage (r=-0.453,P=0.003), and histological grade (r=-0.290,P=0.046). Skp2 expression was inversely correlated with p27(kip1) in prostate cancer (rho=-0.572,P< 0.001).
Expression of Skp2 protein may lead to decrease p27(kip1) level in human prostatic carcinoma, indicating its involvement in the development of human prostatic carcinoma. It may provide new targets for the therapy of prostate cancer.
F-box蛋白Skp2是细胞周期蛋白依赖性激酶抑制剂p27（kip1）泛素介导的蛋白水解所必需的。Skp2在包括乳腺癌、胃癌和前列腺癌在内的多种癌症中均有过表达的报道。本研究旨在探讨Skp2和p27（kip1）表达与前列腺癌临床病理特征的相关性，以及Skp2和p27（kip1）在前列腺癌中的表达相关性。
采用免疫组织化学（EnVision法）对41例人前列腺癌组织及20例良性前列腺增生（BPH）组织中的Skp2和p27（kip1）蛋白表达进行评估。
前列腺癌中Skp2标记频率（8.52%±2.40%）显著高于BPH（0.21%±0.15%）（P<0.001）。前列腺癌中Skp2蛋白表达与术前血清前列腺特异性抗原水平呈正相关（r=0.360，P=0.021），与前列腺外侵犯呈正相关（r=0.570，P<0.001），与肿瘤分期呈正相关（r=0.531，P<0.001），与组织学分级呈正相关（r=0.514，P=0.001）。前列腺癌中p27（kip1）标记频率（70.71%±4.25%）显著低于BPH（97.21%±2.10%）（P<0.001）。前列腺癌中p27（kip1）蛋白表达与术前血清前列腺特异性抗原水平呈负相关（r=-0.399，P=0.010），与前列腺外侵犯呈负相关（r=-0.329，P=0.036），与肿瘤分期呈负相关（r=-0.453，P=0.003），与组织学分级呈负相关（r=-0.290，P=0.046）。在前列腺癌中Skp2表达与p27（kip1）呈负相关（rho=-0.572，P<0.001）。
Skp2蛋白表达可能导致人前列腺癌中p27（kip1）水平降低，表明其参与了人前列腺癌的发生发展。它可能为前列腺癌的治疗提供新的靶点。
