Wang Qingying, Li Yue, Zhou Jianhong, Liu Jie, Qin Jinlong, Xing Feng, Zhang Jiawen, Cheng Jiajing
Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Middle Road, Shanghai, 200072, China.
Tumour Biol. 2015 Jun;36(6):4509-18. doi: 10.1007/s13277-015-3095-x. Epub 2015 Jan 21.
Sam68 (Src-associated in mitosis of 68 kDa) is a substrate for tyrosine kinase c-Src during mitosis. The nuclear protein level has been found to be associated with progression and prognosis in various human malignant tumors. The aim of this study is to investigate the clinical value of Sam68 in endometrial carcinoma (EC). Sam68 expression was confirmed by real-time PCR, Western blot, and immunofluorescent assay in primary normal endometrial epithelial cells, endometrial carcinoma cell lines, as well as seven pairs of EC and matched adjacent noncancerous endometrial tissues. Moreover, the protein level of Sam68 was evaluated by immunohistochemistry in a cohort of surgical specimens derived from 131 patients including primary endometrial carcinoma (n = 95), endometrial atypical hyperplasia (precancerous lesions, n = 26), and normal endometria (n = 10). In endometrial cancer cell lines, RNA interfering approach was employed to downregulate Sam68 expression to determine its role in proliferation. Clinicopathological relevance and prognostic associations were examined by statistical analyses. Compared with normal endometrial and endometrial atypical hyperplasia tissues, Sam68 significantly elevated in endometrial cancer samples (P < 0.01), which was negative or low in 37 cases (38.9 %) and high in 58 cases (61.1 %). The high expression of Sam68 was associated with histological grade (P < 0.001), FIGO stage (P = 0.039), and myometrial invasion (P = 0.002). Kaplan-Meier analysis demonstrated that overexpression of Sam68 correlated with shorter overall survival. It is confirmed by univariate and multivariate analysis (P < 0.001 and P = 0.048, respectively). Additionally, we found that Sam68 was highly expressed at both the transcriptional and translational levels in endometrial cancer cell lines (Ishikawa, HEC-1B, AN3CA, KLE, and RL95-2) and siRNA knockdown of Sam68 remarkably inhibited cellular proliferation in in vitro models. Sam68 may be useful prognostic marker for EC, and it plays an important role in promoting the cellular proliferation. Further investigation of Sam68 as a potential therapeutic target for EC patients could be of interest.
Sam68（68 kDa有丝分裂相关的Src结合蛋白）是有丝分裂期间酪氨酸激酶c-Src的底物。已发现该核蛋白水平与多种人类恶性肿瘤的进展和预后相关。本研究旨在探讨Sam68在子宫内膜癌（EC）中的临床价值。通过实时PCR、蛋白质印迹法和免疫荧光测定法，在原发性正常子宫内膜上皮细胞、子宫内膜癌细胞系以及7对EC及其配对的相邻非癌子宫内膜组织中证实了Sam68的表达。此外，通过免疫组织化学评估了131例手术标本中Sam68的蛋白水平，这些标本包括原发性子宫内膜癌（n = 95）、子宫内膜非典型增生（癌前病变，n = 26）和正常子宫内膜（n = 10）。在子宫内膜癌细胞系中，采用RNA干扰方法下调Sam68表达以确定其在增殖中的作用。通过统计分析检查临床病理相关性和预后关联。与正常子宫内膜和子宫内膜非典型增生组织相比，Sam68在子宫内膜癌样本中显著升高（P < 0.01），其中37例（38.9%）为阴性或低表达，58例（61.1%）为高表达。Sam68的高表达与组织学分级（P < 0.001）、国际妇产科联盟（FIGO）分期（P = 0.039）和肌层浸润（P = 0.002）相关。Kaplan-Meier分析表明，Sam68的过表达与总生存期缩短相关。单因素和多因素分析均证实了这一点（分别为P < 0.001和P = 0.048）。此外，我们发现Sam68在子宫内膜癌细胞系（Ishikawa、HEC-1B、AN3CA、KLE和RL95-2）的转录和翻译水平均高表达，并且在体外模型中，Sam68的siRNA敲低显著抑制细胞增殖。Sam68可能是EC有用的预后标志物，并且在促进细胞增殖中起重要作用。进一步研究Sam68作为EC患者潜在的治疗靶点可能具有重要意义。
