Hwang Tae Sook, Han Hye Seung, Choi Hyo Kyoung, Lee Yong J, Kim Yun-Jeong, Han Mi-Young, Park Young-Mee
Department of Pathology, Inha University College of Medicine, Incheon, Korea.
J Gastroenterol Hepatol. 2003 Jun;18(6):690-700. doi: 10.1046/j.1440-1746.2003.03011.x.
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.
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.
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.
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.
实体瘤中缺氧细胞的存在被认为与多种肿瘤的恶性进展有关。最近，我们报道了缺氧可激活小鼠肿瘤细胞中的热休克转录因子（HSF）并诱导热休克蛋白（Hsp）的表达。
为了探寻Hsp在人类肿瘤恶性进展中的可能作用，我们分析了低转移和高转移人结肠直肠癌（CRC）细胞系中Hsp家族蛋白的表达谱。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多种实体瘤中得到证实。
在本文中，我们发现在各种Hsp和Bcl-2家族蛋白中，Hsp70和Hsp110的表达在高转移的CX-1和HT-29细胞中升高，而Bcl-2的表达在低转移的MIP-101和Clone A细胞中升高。随后对81例原发性人类CRC组织进行的免疫组织化学分析表明，Hsp70和Hsp110的表达与临床晚期和阳性淋巴结受累高度相关。相比之下，Bcl-2的表达与临床早期和阴性淋巴管浸润相关。
综上所述，我们的研究首次证明了Hsp70、Hsp110和Bcl-2在CRC中存在差异的、依赖分期的表达。我们认为，Hsp和Bcl-2家族成员差异表达的分子机制值得未来进行更深入的研究，其结果可能会为预测和控制结肠直肠癌的恶性进展提供新的理论依据和策略。
