The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlates with the reduced p16INK4a/p14ARF proteins

To clarify the roles of Bmi-1 in colorectal carcinoma, we examined the expression of Bmi-1 in 41 samples out of 46 colorectal carcinomas by reverse transcription-PCR, whereas all 46 were analyzed by immunostaining. In addition, we analyzed the expression patterns of Bmi-1 in association with p16INK4a and p14ARF (in mouse p19ARF) in a series of colorectal carcinomas. The level of Bmi-1 mRNA in he carcinoma tissues was significantly higher than those of the adjacent non-neoplastic colonic mucosal tissues. Immunohistochemistry for Bmi-1 showed moderate or strong expression levels in 65% (30/46) of colorectal carcinomas. Colorectal carcinomas with moderate or strong Bmi-1 expression were more likely to have low levels of the INK4 locus proteins (p16INK4a/p14ARF) (P < 0.07). These results suggested that modulation of Bmi-1 protein might be involved in human colorectal carcinogenesis by repressing the INK4a/ARF proteins. (C) 2003 Elsevier Ireland Ltd. All rights reserved.