Expression of SIP1 in oral squamous cell carcinomas: implications for E-cadherin expression and tumor progression.
Expression of SIP1 in oral squamous cell carcinomas: implications for E-cadherin expression and tumor progression.
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DOI：
10.3892/ijo.27.6.1535
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发表时间：
2005-12
影响因子：
5.2
通讯作者：
G. Maeda;T. Chiba;M. Okazaki;T. Satoh;Y. Taya;T. Aoba;K. Kato;S. Kawashiri;K. Imai
中科院分区：
文献类型：
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作者：
G. Maeda;T. Chiba;M. Okazaki;T. Satoh;Y. Taya;T. Aoba;K. Kato;S. Kawashiri;K. Imai
E-cadherin表达的缺失允许癌细胞从原发部位释放并增强侵袭和转移。E-cadherin的遗传畸变在散发性肿瘤中是罕见的，转录抑制因子被认为在E-cadherin的丢失中起着重要作用。然而，E-钙粘蛋白阻遏物的表达在很大程度上取决于组织和细胞类型。为了确定口腔鳞癌中表达的阻遏物，我们通过实时荧光定量RT-PCR比较了E-cadherin和阻遏物的表达水平。在SNAIL、SLUG、SIP 1、E12和E47等抑制因子中，SIP 1与E-cadherin呈负相关（P < 0.05）。染色质免疫沉淀显示SIP 1特异性结合于E-cadherin启动子区。47例口腔癌中SIP 1阳性表达率为27.7%，而SIP 1阳性表达者E-cadherin均不表达（P < 0.01）。13例SIP 1阳性患者的疾病特异性生存率较低（P < 0.05）。多因素分析显示SIP 1表达是影响预后的独立危险因素（P < 0.05）。这些结果表明，SIP 1有助于E-cadherin表达的损失，SIP 1表达的检测是一个预测和预后的工具，在口腔癌的临床管理。
Loss of E-cadherin expression allows carcinoma cells to liberate from the primary site and enhances invasion and metastasis. The genetic aberration of E-cadherin is a rare event in sporadic carcinomas, and transcription repressors are considered to take a central role in E-cadherin loss. However, expression of E-cadherin repressors is largely dependent on tissue and cell type. To identify the repressor expressed in oral squamous carcinomas, we compared the expression levels of E-cadherin and repressors by real-time RT-PCR. Among the repressors including SNAIL, SLUG, SIP1, E12 and E47, SIP1 was inversely correlated to E-cadherin (P < 0.05). Chromatin immunoprecipitation showed that SIP1 specifically bound to the E-cadherin promoter region. SIP1 expression was immuno-histochemically detected in 27.7% of 47 oral carcinomas, and SIP1-positive carcinomas did not express E-cadherin (P < 0.01). Thirteen patients with SIP1 staining showed a lower disease-specific survival rate (P < 0.05). Multivariate risk factor analysis demonstrated that SIP1 expression was an independent prognostic value for disease-specific overall survival (P < 0.05). These results suggest that SIP1 contributes to the loss of E-cadherin expression and that detection of SIP1 expression is a predictive and prognostic tool in clinical management of oral carcinomas.