Loss of SIRT1 histone deacetylase expression associates with tumour progression in colorectal adenocarcinoma

Journal of Clinical Pathology
Si-Hyong JangKi-Seok Jang

Abstract

The class III histone deacetylase SIRT1 is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, and has been reported to serve diverse roles in various biological processes, such as caloric restriction, apoptosis, neuronal protection, cell growth, differentiation and tumourigenesis. With respect to tumourigenesis, there have been conflicting data supporting whether SIRT1 act as a tumour promoter or as a tumour suppressor. SIRT1 protein expression, determined by immunohistochemistry, was investigated in human normal colonic mucosa, adenoma, adenocarcinoma and metastatic tissue samples. All normal colonic mucosa showed SIRT1 expression with no exception, and 42 (80.8%) of 52 adenomatous polyps were positive for SIRT1. However, only 208 (41.9%) of 497 colorectal adenocarcinomas were positive. Moreover, 45 (35.7%) of 126 metastatic tissues were positive. Collectively, the SIRT1 expression was gradually decreased during carcinogenesis and tumour progression. The associations between SIRT1 expression and clinicopathological parameters revealed that loss of SIRT1 expression was associated with proximal tumour location, mucinous histology and defective mismatch repair protein expression. This suggests that loss of SIRT1 ...Continue Reading

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