Intracellular localization of survivin determines biological behavior in colorectal cancer
Intracellular localization of survivin determines biological behavior in colorectal cancer
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DOI：
10.3892/or_00000471
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发表时间：
2009-09-01
期刊：
影响因子：
4.2
通讯作者：
Shimamoto, Fumio
中科院分区：
文献类型：
--
作者：
Qi, Guangying;Tuncel, Handan;Shimamoto, Fumio
生存素是一种抑制细胞凋亡和调节细胞分裂的双功能蛋白，在多种人类癌症中高度表达。近年来，生存素在肿瘤细胞内的定位已被认为是一种预后指标，但其分子机制尚不清楚。本研究旨在探讨Survivin在结直肠癌中的表达及其与临床病理因素和患者生存期的关系。142例进展期结直肠癌组织中Survivin蛋白表达阳性率为76.8%（109/142），胞浆阳性率为20.4%（29/142）。细胞质Survivin过表达与预后不良相关，但细胞核Survivin过表达与预后较好相关。Western blotting进一步证实了5例大肠癌患者非固定标本新鲜活检的癌组织或周围正常组织中Survivin的亚细胞分布。Survivin主要存在于不溶性部分中。有趣的是，不管不溶性部分中的存活素蛋白水平如何，具有表达胞质和核可溶性存活素的癌组织的患者遭受淋巴结转移。这些数据表明，细胞质中的生存素的功能可能是重要的恶性进展和细胞质和核可溶性生存素的水平可能是更相关的预后因素，结直肠癌比生存素的总量。
Survivin is a bifunctional protein that suppresses apoptosis and regulates cell division and is highly expressed in various human cancers. Recently, the intracellular localization of survivin in tumors has been suggested as a prognostic marker, but the molecular mechanisms are not understood. The aims of the present study were to investigate the different localization of survivin expression in colorectal carcinoma and expression of survivin relationships with clinicopathological factors and patient survival. Immunohistochemical analyses of 142 cases of advanced colorectal cancer showed that 109 (76.8%) cases expressed survivin in the nucleus and 29 cases (20.4%) in the cytoplasm. Cytoplasmic survivin overexpression was associated with a poor prognosis, but nuclear survivin overexpression was associated with a better prognosis. Subcellular distribution of survivin in five cases of cancerous or surrounding normal tissues derived from fresh biopsy of non-fixed samples of colorectal cancer patients was further demonstrated by Western blotting. Survivin was primarily found in the insoluble fraction. Interestingly, regardless of survivin protein levels in the insoluble fraction, patients who had cancerous tissue expressing cytoplasmic and nuclear soluble survivin suffered from lymph nodes metastases. These data suggest that the function of cytoplasmic survivin might be important for malignant progress and the levels of cytoplasmic and nuclear soluble survivin might be more relevant for prognostic factors for colorectal cancer than the total amount of survivin.