Gankyrin oncoprotein overexpression as a critical factor for tumor growth in human esophageal squamous cell carcinoma and its clinical significance
Gankyrin oncoprotein overexpression as a critical factor for tumor growth in human esophageal squamous cell carcinoma and its clinical significance
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DOI：
10.1002/ijc.23106
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发表时间：
2008-01-15
影响因子：
6.4
通讯作者：
Shimada, Yutaka
中科院分区：
文献类型：
--
作者：
Ortiz, Cristian M.;Ito, Tetsuo;Shimada, Yutaka
为了阐明gankyrin可能参与ESCC的进展及其下调在ESCC中的作用，我们研究了gankyrin在ESCC组织中的表达，并将其与相应的正常食管上皮细胞进行了比较，并检测了短发夹RNA （shRNA）在ESCC细胞系中的表达载体。采用RT-PCR和western blot方法检测11株ESCC细胞株（KYSE系）中Gankyrin蛋白的表达。采用Real-time PCR法比较30例ESCC组织与正常上皮组织中gankyrin mRNA的表达情况。用免疫组织化学方法分析103例ESCC中gankyrin蛋白的表达。将gankyrin- shrna载体稳定转染到KYSE 170细胞中，评估gankyrin在细胞运动、体外侵袭增殖和体内肿瘤形成中的作用。11种ESCC细胞系中Gankyrin表达均升高。实时荧光定量PCR结果显示，所有30例患者癌组织中gankyrin的表达均较高。在免疫组织化学中，gankyrin过表达与生存率（p = 0.0001）、原发肿瘤范围、淋巴结转移、远处淋巴结转移和分期（p = 0.0072、p = 0.0004、p = 0.0172和p = 0.0002）降低相关。抗gankyrin的shRNA载体在体外抑制生长、细胞运动、侵袭性和体内肿瘤形成。Gankyrin过表达与预后不良相关。它可能在ESCC肿瘤进展中起重要作用，可能是ESCC潜在的重要治疗基因靶点。(C) 2007 Wiley-Liss, Inc。
To elucidate the possible involvement of gankyrin in ESCC progression and the effect of its down-regulation in ESCC, we investigated the expression of gankyrin in ESCC tissues comparing it with the corresponding normal esophageal epithelia and tested a short-hairpin RNA (shRNA) expression vector for gankyrin in ESCC cell lines. Gankyrin protein expression in 11 ESCC cell lines (KYSE series) was examined by RT-PCR and western blot. The expression of gankyrin mRNA in 30 ESCC tissues was compared with the corresponding normal epithelia by Real-time PCR. Expression of gankyrin protein was immunohistochemically analyzed in the ESCC of 103 patients. A gankyrin-shRNA vector was stably transfected into KYSE 170 cells to assess the role of gankyrin in cell motility, invasion and proliferation in vitro and tumor formation in vivo. Gankyrin expression increased in all 11 ESCC cell lines. Real-time PCR revealed that gankyrin expression was higher in the cancerous tissue for all 30 patients. In immunohistochemistry, gankyrin overexpression was correlated with lower survival rate (p = 0.0001), extent of the primary tumor, lymph node metastasis, distant lymph node metastasis and stage (p = 0.0072, p = 0.0004, p = 0.0172 and p = 0.0002, respectively). A shRNA vector against gankyrin repressed growth, cell motility, invasiveness in vitro and tumor formation in vivo. Gankyrin overexpression is associated with poor prognosis. It may play an important role in ESCC tumor progression and could be a potentially important therapeutic gene target in ESCC. (C) 2007 Wiley-Liss, Inc.