Ma Xiu-Mei, Liu Jiang-Hui, Guo Jian-Wen, Liu Ying, Zuo Lian-Fu
Hebei Provincial Tumor Institute, The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei 050011, P. R. China.
Ai Zheng. 2006 Jan;25(1):56-61.
BACKGROUND & OBJECTIVE: S-phase kinase-associated protein 2 (Skp2) is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of cyclin-dependent kinase inhibitor P27. Its overexpression has been involved in cell transformation and tumorigenesis. This study was to investigate the significance of Skp2 expression in human gastric carcinoma and its correlation to expression of both P27 and PTEN.
The expression of Skp2 in 138 specimens of gastric cancer and their paired adjacent mucosa, 102 specimens of paired metastatic lymph nodes, 30 specimens of dysplasia, 30 specimens of intestinal metaplasia, 10 specimens of chronic superficial gastritis, and 5 specimens of normal gastric mucosa, and the expression of P27 and PTEN in 138 specimens of gastric cancer were detected by immunohistochemistry.
Skp2 labeling frequency was significantly higher in intestinal metaplasia [(12.68+/-0.86)%] and adjacent mucosa [(19.32+/-1.22)%] than in chronic superficial gastritis [(0.53+/-0.13)%] and normal gastric mucosa [(0.47+/-0.19)%] (P<0.001), but there was no difference between chronic superficial gastritis and normal gastric mucosa (P>0.05); Skp2 labeling frequency was significantly higher in dysplasia [(16.74+/-0.82)%] than in intestinal metaplasia (P<0.001), significantly higher in primary gastric carcinoma [(31.34+/-2.17)%] than in dysplasia and adjacent mucosa (P<0.001), and significantly higher in metastatic lymph node [(39.76+/-2.00)%] than in primary gastric carcinoma (P=0.037). Skp2 labeling frequency in gastric carcinoma was positively correlated with differentiation grade (rs=0.315, P<0.001), vessel invasion (rs=0.303, P<0.001), and lymph node metastasis (rs=0.254, P=0.001). Skp2 expression was negatively correlated with both P27 expression (rs=-0.451, P<0.001) and PTEN expression (rs=-0.480, P<0.001) in gastric carcinoma. P27 expression was positively correlated with PTEN expression in gastric carcinoma (rs=0.642, P<0.001).
Skp2 overexpression, which may lead to degradation of P27 and low expression of PTEN, may be a very important reason in carcinogenesis and progression of gastric carcinoma.
S期激酶相关蛋白2（Skp2）是G1-S期转换的正向调节因子，可促进细胞周期蛋白依赖性激酶抑制剂P27的泛素介导的蛋白水解。其过表达与细胞转化和肿瘤发生有关。本研究旨在探讨Skp2在人胃癌中的表达意义及其与P27和PTEN表达的相关性。
采用免疫组织化学法检测138例胃癌及其配对的癌旁黏膜、102例配对的转移淋巴结、30例发育异常组织、30例肠化生组织、10例慢性浅表性胃炎组织和5例正常胃黏膜组织中Skp2的表达，以及138例胃癌组织中P27和PTEN的表达。
Skp2标记频率在肠化生组织[（12.68±0.86）%]和癌旁黏膜[（19.32±1.22）%]中显著高于慢性浅表性胃炎组织[（0.53±0.13）%]和正常胃黏膜组织[（0.47±0.19）%]（P<0.001），但慢性浅表性胃炎组织与正常胃黏膜组织之间无差异（P>0.05）；Skp2标记频率在发育异常组织[（16.74±0.82）%]中显著高于肠化生组织（P<0.001），在原发性胃癌组织[（31.34±2.17）%]中显著高于发育异常组织和癌旁黏膜（P<0.001），在转移淋巴结组织[（39.76±2.00）%]中显著高于原发性胃癌组织（P=0.037）。胃癌组织中Skp2标记频率与分化程度（rs=0.315，P<0.001）、血管侵犯（rs=0.303，P<0.001）和淋巴结转移（rs=0.254，P=0.001）呈正相关。胃癌组织中Skp2表达与P27表达（rs=-0.451，P<0.001）和PTEN表达（rs=-0.480，P<0.001）均呈负相关。胃癌组织中P27表达与PTEN表达呈正相关（rs=0.642，P<0.001）。
Skp2过表达可能导致P27降解和PTEN低表达，可能是胃癌发生和进展的重要原因。
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