Characterization and over-expression of chaperonin t-complex proteins in colorectal cancer

被引:94
作者
Coghlin, C.
Carpenter, B.
Dundas, S. R.
Lawrie, L. C.
Telfer, C.
Murray, G. I.
机构
[1] Univ Aberdeen, Dept Pathol, Aberdeen AB25 2ZD, Scotland
[2] Auvat Ltd, Aberdeen, Scotland
关键词
colorectal cancer; immunohistochemistry; proteomics; TCP1; beta; t-complex polypeptide-1; epsilon; tissue microarray;
D O I
10.1002/path.2056
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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, TCPI beta cellular localization was exclusively cytoplasmic, whereas TCPI epsilon staining was seen in both the nucleus and the cytoplasm. Both cytoplasmic TCPI 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 TCPI beta and reduced patient survival (p=0.05). These results show that both TCPI beta and TCP1 epsilon are over-expressed in colorectal cancer and indicate a role for TCP1 beta and TCP1 epsilon in colorectal cancer progression. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
引用
收藏
页码:351 / 357
页数:7
相关论文
共 27 条
[1]  
Bendardaf R, 2004, ANTICANCER RES, V24, P2519
[2]   Mortalin is over-expressed by colorectal adenocarcinomas and correlates with poor survival [J].
Dundas, SR ;
Lawrie, LC ;
Rooney, PH ;
Murray, GI .
JOURNAL OF PATHOLOGY, 2005, 205 (01) :74-81
[3]   Substantial CCT activity is required for cell cycle progression and cytoskeletal organization in mammalian cells [J].
Grantham, Julie ;
Brackley, Karen I. ;
Willison, Keith R. .
EXPERIMENTAL CELL RESEARCH, 2006, 312 (12) :2309-2324
[4]   Diverse effects of mutations in Exon II of the von Hippel-Lindau (VHL) tumor suppressor gene on the interaction of pVHL with the cytosolic chaperonin and pVHL-dependent ubiquitin ligase activity [J].
Hansen, WJ ;
Ohh, M ;
Moslehi, J ;
Kondo, K ;
Kaelin, WG ;
Welch, WJ .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (06) :1947-1960
[5]   A Dictyostelium discoideum homologue to Tcp-1 is essential for growth and development [J].
Iijima, M ;
Shimizu, H ;
Tanaka, Y ;
Urushihara, H .
GENE, 1998, 213 (1-2) :101-106
[6]  
KUBOTA H, 1995, EUR J BIOCHEM, V230, P3, DOI 10.1111/j.1432-1033.1995.0003i.x
[7]  
KUBOTA H, 1992, GENE, V120, P207, DOI 10.1016/0378-1119(92)90095-7
[8]   Cytochrorne P450 profile of colorectal cancer: Identification of markers of prognosis [J].
Kumarakulasingham, M ;
Rooney, PH ;
Dundas, SR ;
Telfer, C ;
Melvin, WT ;
Curran, S ;
Murray, GI .
CLINICAL CANCER RESEARCH, 2005, 11 (10) :3758-3765
[9]   Spot the differences: proteomics in cancer research [J].
Lawrie, Laura C. ;
Fothergill, John E. ;
Murray, Graeme, I .
LANCET ONCOLOGY, 2001, 2 (05) :270-277
[10]   Liver fatty acid binding protein expression in colorectal neoplasia [J].
Lawrie, LC ;
Dundas, SR ;
Curran, S ;
Murray, GI .
BRITISH JOURNAL OF CANCER, 2004, 90 (10) :1955-1960