GENETIC STATUS AND EXPRESSION OF THE CYCLIN-DEPENDENT KINASE INHIBITORS IN HUMAN GASTRIC-CARCINOMA CELL-LINES

Deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhi bitors could have a pivotal role in the development of diverse human c ancers. We examined the genetic status and the expression of CDK inhib itors (p21, p27, p16 and p15), CDK2 and cyclins (A, D1 and E) in eight gastric carcinoma cell lines, in comparison with the status of p53 ge ne alterations. All the cell lines (except MKN-28) that contained a p5 3 gene abnormality expressed very low or undetectable levels of p21 mR NA, while the cell lines (MKN-45 and -74) with wild-type p53 gene expr essed high levels of p21 mRNA. An inverse correlation was found betwee n the level of p21 mRNA and the expression of mRNAs for CDK2 and G1 cy clins. MKN-28 was an exception; it contained mutated p53, and expresse d mRNAs for p21, CDK2 and G1 cyclins at high levels. Only MKN-45 and - 74, with wild-type p53, expressed considerable levels of p21 protein. Homozygous deletion of the p16 and p15 genes was detected in two (MKN- 45 and HSC-39) of the eight gastric carcinoma cell lines. p16 protein was not expressed in three cell lines (MKN-28, MKN-74 and KATO-III), a s well as MKN-45 and HSC-39. Rearrangement of the p15 gene was found i n TMK-1. Rearrangement of the p27 gene was detected in MKN-45, althoug h the expression of p27 protein was well preserved in all the gastric carcinoma cell lines. The expression of pRb was also preserved in all the cell lines except KATO-III. No obvious correlation was observed be tween the p53 gene status and the expression of p27 and p16. These fin dings suggest that abnormal regulation of CDK2/cyclins and CDK inhibit ors might be involved in deregulated growth of gastric carcinomas.