[Mutation, loss of heterozygosity, and expression of tumor suppressor gene ING1 in sporadic colorectal carcinoma]

Abstract

Background & objective: Inhibitor of growth 1 (ING(1)) gene has been identified as a novel tumor suppressor gene. Its over-expression can inhibit cell growth, and induce cell apoptosis. This study was to explore the effect and significance of ING(1) gene in occurrence and progression of sporadic colorectal cancer.

Methods: The expression, mutation, and loss of heterozygosity (LOH) of ING(1) gene in 46 specimens of sporadic colorectal cancer tissues and adjuvant normal mucous membrane tissues were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), PCR-single strain conformation polymorphism (PCR-SSCP), and microsatellite markers, respectively.

Results: (1)The average ratios of light density of p33/ING(1) mRNA, and p47/ING(1) mRNA in the cancerous tissues were significantly lower than those in normal tissues (0.52 vs. 1.28, P < 0.01; 0.51 vs. 1.21, P < 0.01). Difference between the 2 mRNA splices was not significant in the matched tissues (P > 0.05). (2) The average ratios of light density of p33/ING(1) mRNA, and p47/ING(1) mRNA in the cancerous tissues of Dukes' C, D stage were significantly lower than those in cancerous tissues of Dukes' A, B stage (0.38 vs. 0.65, P < 0.01; 0.40 vs. 0.63, P < 0.01). (3) Of the 46 cases, no mutation of ING(1) gene was detected, only 5 (10.9%)cases of LOH were found.

Conclusions: Abnormal alteration of ING(1) gene is rare in sporadic colorectal cancer. Its down-regulation may happen in transcription or post-transcription, and correlates tightly with the occurrence and progression of sporadic colorectal cancer.