Differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer
Differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer
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DOI：
10.1046/j.1440-1746.2003.03011.x
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发表时间：
2003-06-01
影响因子：
4.1
通讯作者：
Park, YM
中科院分区：
文献类型：
--
作者：
Hwang, TS;Han, HS;Park, YM
背景：实体瘤中缺氧细胞的存在被认为是导致各种肿瘤恶性进展的原因。最近，我们报道了热休克转录因子（HSF）的激活和热休克蛋白（Hsp）的表达在小鼠肿瘤细胞缺氧的研究方法：为了寻找热休克蛋白在人类肿瘤的恶性进展中的可能作用，我们分析了热休克蛋白家族蛋白在弱转移和高转移的人结直肠癌（CRC）细胞系的表达谱。我们还分析了Bcl-2家族蛋白的表达谱，因为这些蛋白的表达改变已在各种实体瘤中得到证实。在本论文中，我们发现在各种Hsp和Bcl-2家族蛋白中，Hsp 70和Hsp 110的表达在高转移性CX-1和HT-29细胞中升高，而Bcl-2在MIP-101和克隆A细胞中表达增强。对81例大肠癌组织的免疫组化分析表明，Hsp 70和Hsp 110的表达与大肠癌的临床分期和淋巴结转移密切相关。Bcl-2的表达，相比之下，与早期临床分期和负淋巴血管invasion.Conclusion：两者合计，我们的研究首次证明了一个差异，阶段依赖性表达的Hsp 70，Hsp 110和Bcl-2在CRC。我们认为，热休克蛋白和Bcl-2家族成员的差异表达的分子机制值得更严格的未来研究，其结果可能提供新的模式的理论基础和策略，以预测和操纵结直肠癌的恶性进展。(C)2003年Blackwell Publishing Asia Pty Ltd.
Background: The presence of hypoxic cells in solid tumors has been suggested to contribute to the malignant progression of various tumors. Recently, we reported an activation of heat shock transcription factor (HSF) and expression of heat shock proteins (Hsp) in murine tumor cells by hypoxia.Methods: To search for a possible role of Hsp in the malignant progression of human tumors, we analyzed the expression profiles of Hsp family proteins in weakly and highly metastatic human colorectal cancer (CRC) cell lines. We also analyzed the expression profiles of Bcl-2 family proteins because the altered expression of these proteins has been demonstrated in various solid tumors.Results: In the present paper we showed among various Hsp and Bcl-2 family proteins that the expression of Hsp70 and Hsp110 was elevated in highly metastatic CX-1 and HT-29 cells, while the expression of Bcl-2 was elevated in weakly metastatic MIP-101 and Clone A cells. Subsequent immunohistochemical analysis of 81 primary human CRC tissues demonstrated that the expression of Hsp70 and Hsp110 was highly correlated with the advanced clinical stages and positive lymph node involvement. The expression of Bcl-2, in contrast, was correlated to the early clinical stage and negative lymphovascular invasion.Conclusion: Taken together, our study demonstrated for the first time a differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in CRC. We suggest that the molecular mechanisms underlying the differential expression of Hsp and Bcl-2 family members deserves a more rigorous future study, the results of which might offer novel modes of rationale and strategy to predict and manipulate the malignant progression of colorectal cancers. (C) 2003 Blackwell Publishing Asia Pty Ltd.