Analysis of key cell-cycle checkpoint proteins in colorectal tumours

McKay, J., Douglas, J., Ross, V., Curran, S., Loane, J., Ahmed, F., Cassidy, J., McLeod, H. and Murray, G. (2002) Analysis of key cell-cycle checkpoint proteins in colorectal tumours. Journal of Pathology, 196(4), pp. 386-393. (doi: 10.1002/path.1053)

Abstract

Aberrations in the components of cell-cycle checkpoints are a common feature of many tumours and several have been shown to have prognostic significance in colorectal cancer. In this study, seven components of cell-cycle control [cyclin D1, retinoblastoma (pRb), p21, p27, p16, p53, and proliferating cell nuclear antigen (PCNA)l were examined in a large series of well-characterized colorectal adenocarcinomas using immunohistochemistry to ascertain co-regulation and influence on survival. The majority (92%) of the tumours had abnormal staining of greater than or equal to 2 cell-cycle control factors. Expression of cyclin D1 protein was correlated with both p21 (p<0.001) and p27 (p=0.033), suggesting co-regulation of these proteins in colorectal tumours. Only cyclin D1 (p=0.048) and p53 (p=0.025) were directly associated with PCNA levels, suggesting a more important role in the proliferative capacity of tumour cells. Significant associations between cell cycle-related proteins and clinicopathological data were observed: cyclin D1 and p53 proteins were correlated with patient age (p=0.042 and p<0.001, respectively) and p53 (p=0.01) and p21 (p=0.024) proteins were associated with tumour site. Expression of cyclin D1 protein was the only protein examined that was related to improved outcome in these patients (p=0.0266), but it was not an independent predictor of survival. These results suggest that loss of control of ell-cycle checkpoints is a common occurrence in colorectal tumours and may be an important 1 therapeutic target.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cassidy, Professor James
• Authors: McKay, J., Douglas, J., Ross, V., Curran, S., Loane, J., Ahmed, F., Cassidy, J., McLeod, H., and Murray, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Pathology
• ISSN: 0022-3417