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热休克蛋白70(HSP70)在结直肠癌患者中的表达——免疫组织化学和蛋白质印迹分析

Expression of heat shock protein 70 (HSP70) in patients with colorectal adenocarcinoma--immunohistochemistry and Western blot analysis.

作者信息

Milićević Z T, Petković M Z, Drndarević N C, Pavlović M D, Todorović V N

机构信息

Institute of Nuclear Sciences Vinca, Laboratory for Molecular Biology and Endocrinology, Belgrade, Serbia and Montenegro.

出版信息

Neoplasma. 2007;54(1):37-45.

Abstract

The role of heat shock protein 70 (HSP70) expression has been investigated in various types of tumors. There are only little and controversial data about its clinical relevance in colorectal carcinoma, one of the most common carcinomas observed in humans. In this study we investigated expression of HSP70 in human colonic carcinoma and possible correlation with clinicopathology. To assess patterns (cytosolic and membrane) of HSP70 expression, the 48 surgically removed colorectal adenocarcinomas and 12 normal colonic and rectal mucosal samples were examined by immunohistochemistry and Western-blot. According to results of immunohistochemistry, expression of cytoplasmic HSP72 was significantly higher in colorectal carcinoma compared with normal and adjacent mucosa (p<0.01). In addition, there was significant increase in HSP72 expression in lymph node-positive compared to node-negative group (p<0.001). Dukes C2 stage of colonic cancer showed significantly higher immunohistochemical score than Dukes B2 and B1 stage groups (p< 0.05 i.e. p< 0.02). There was no relation between expression of HSP72 and degree of tumor differentiation. Using Western blot analyses, we noticed elevated levels of cytosolic HSP70 in colorectal cancer cells compared to normal. Densitometric analysis of blots of plasma membrane HSP70 expression has shown decrease in colorectal cancer cells compared to normal mucosa. According to our results, overexpression of HSP72 in malignant tissues of patients with colorectal carcinoma is related to tumor progression, suggesting that these proteins could play an important role not only in tumorigenesis but also in the development of drug resistance. Further research is necessary to clarify the mechanisms responsible for differential HSP70 expression as well as its definitive role in colorectal cancer.

摘要

热休克蛋白70(HSP70)表达在各类肿瘤中的作用已得到研究。关于其在结直肠癌(人类最常见的癌症之一)中的临床相关性,仅有少量且存在争议的数据。在本研究中,我们调查了HSP70在人类结肠癌中的表达及其与临床病理的可能相关性。为评估HSP70表达模式(胞质和膜性),采用免疫组织化学和蛋白质印迹法检测了48例手术切除的结直肠腺癌以及12例正常结肠和直肠黏膜样本。根据免疫组织化学结果,结直肠癌中细胞质HSP72的表达显著高于正常及相邻黏膜(p<0.01)。此外,与淋巴结阴性组相比,淋巴结阳性组中HSP72的表达显著增加(p<0.001)。结肠癌的Dukes C2期免疫组织化学评分显著高于Dukes B2和B1期组(p<0.05即p<0.02)。HSP72的表达与肿瘤分化程度无关。通过蛋白质印迹分析,我们注意到与正常细胞相比,结直肠癌细胞中胞质HSP70水平升高。对质膜HSP70表达印迹的光密度分析显示,与正常黏膜相比,结直肠癌细胞中的表达降低。根据我们的结果,结直肠癌患者恶性组织中HSP72的过表达与肿瘤进展相关,提示这些蛋白不仅在肿瘤发生中,而且在耐药性发展中可能发挥重要作用。有必要进一步研究以阐明HSP70差异表达的机制及其在结直肠癌中的明确作用。

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