Coghlin C, Carpenter B, Dundas S R, Lawrie L C, Telfer C, Murray G I
Department of Pathology, University of Aberdeen, Aberdeen, UK.
J Pathol. 2006 Nov;210(3):351-7. doi: 10.1002/path.2056.
The chaperonins are key molecular complexes, which are essential in the folding of proteins to produce stable and functionally competent protein conformations. One member of the chaperonin group of proteins is TCP1 (chaperonin containing t-complex polypeptide 1, or CCT), but little is known about this protein in tumours. In this study, we used comparative proteomic analysis to show that t-complex protein subunits TCP1 beta and TCP1 epsilon are over-expressed in colorectal adenocarcinomas. Monoclonal antibodies to these proteins were developed and the expression and cellular localization of these two proteins in colorectal cancer were analysed by immunohistochemistry on a colorectal cancer tissue microarray. In colorectal cancer, TCP1 beta cellular localization was exclusively cytoplasmic, whereas TCP1 epsilon staining was seen in both the nucleus and the cytoplasm. Both cytoplasmic TCP1 beta and cytoplasmic TCP1 epsilon were significantly over-expressed (p < 0.001 for each protein) in primary colorectal cancer and also showed increased expression with advancing Dukes' stage (p = 0.018 for TCP1 beta and p = 0.045 for TCP1 epsilon). A trend was also identified between over-expression of cytoplasmic TCP1 beta and reduced patient survival (p = 0.05). These results show that both TCP1 beta and TCP1 epsilon are over-expressed in colorectal cancer and indicate a role for TCP1 beta and TCP1 epsilon in colorectal cancer progression.
伴侣蛋白是关键的分子复合物,对于蛋白质折叠以产生稳定且具有功能活性的蛋白质构象至关重要。伴侣蛋白家族中的一个成员是TCP1(含t-复合体多肽1的伴侣蛋白,或CCT),但关于该蛋白在肿瘤中的情况知之甚少。在本研究中,我们通过比较蛋白质组学分析表明,t-复合体蛋白亚基TCP1β和TCP1ε在结直肠癌中过度表达。我们制备了针对这些蛋白的单克隆抗体,并通过对结直肠癌组织芯片进行免疫组织化学分析,研究了这两种蛋白在结直肠癌中的表达及细胞定位。在结直肠癌中,TCP1β仅定位于细胞质,而TCP1ε在细胞核和细胞质中均有染色。细胞质中的TCP1β和TCP1ε在原发性结直肠癌中均显著过度表达(每种蛋白p < 0.001),并且随着Dukes分期的进展表达增加(TCP1β为p = 0.018,TCP1ε为p = 0.045)。还发现细胞质TCP1β过度表达与患者生存率降低之间存在一种趋势(p = 0.05)。这些结果表明,TCP1β和TCP1ε在结直肠癌中均过度表达,并提示TCP1β和TCP1ε在结直肠癌进展中发挥作用。