| [ Summary ] |
The adenoma-carcinoma sequence in colon tumors was closely studied and several genes. associated with early tumorigenesis were discovered. Each, genetically mutated with additional time (APC/K-ras/DCC/p53). The deregulation of apoptosis is also involved in the pathogenesis of colon tumors. The fragile histidine triad (FHIT) gene is involved in deletions on the short arm of chromosome 3 in various human cancers. We found that 47% of colorectal adenomas, which is a higher frequency rate than that for K-ras, showed an altered expression of the Fhit protein, as seen with the Western blot analysis. Our results suggest that altered expression of the FHIT gene is a quite early aberration in the development of colorectal tumors and that the Fhit protein may act as a tumor suppressor. The RCK gene was cloned through the study of the breakpoint of the t (11 ; 14)(q23 ; q32) chromosomal translocation, observed in human B-cell lymphoma. The rck/p54 protein belongs to the DEAD box protein/RNA helicase family, which has a variety of functions, such as translation initiation, pre-mRNA splicing, and ribosome assembly. It is thought that the rck/p54 protein may have a great effect on the mRNA structure of genes associated with cell proliferation and facilitate their protein synthesis. The rck/p54 protein was found to be over expressed in tumor tissues resected from 65.4% of colorectal adenomas, and 93% of these positive cases also co-overexpressed c-myc protein. rck/p54 may contribute to cell proliferation and carcinogenesis at the translational level by increasing the synthesis of c-myc protein in the development of human colorectal tumors. Thus, the inactivation of anti-oncogenes and activation of on cogenes disturbes the regulation of apoptosis, with the result that the possibility of tumorigenesis may be increased. |