Correlation between p21(waf1) and p16(INK4 alpha) expression in hepatocellular carcinoma

Background: The cyclin dependent kinase p21(waf1) plays a crucial role in t he regulation of cell cycle. The family of p53 proteins has the ability to induce p21(waf1), whereas p16(INK4 alpha) modulates post-transcriptionally the expression of p21(waf1). Methods: Total 36 hepatocellular carcinomas (H CCs) and 24 paired adjacent liver tissues were evaluated for the following: (1) expression of p21(waf1) and p16(INK4 alpha); (2) that of p21(waf1), p7 3 and p63 mRNAs; (3) genomic mutations and the loss of heterozygosity of p7 3 and p53; and (4) frequency of methylation in the 5'CpG promoter region of p16(INK4 alpha). Results: In HCCs compared with the adjacent non-cancerous liver tissues, the expression of p21(waf1) and p16(INK4 alpha) was reduced . Indeed, p21(waf1) was not detected in 36% (8/22) of HCCs in spite of the presence of p21(waf1) mRNA: among them, mutations of p53 gene were found in 50%, whereas a lack of p16(INK4 alpha) expression in all of them. p21(waf1 ) and p16(INK4 alpha) were reduced in proportion to the degree of methylati on in p16(INK4 alpha) gene, p73 did not mutated, and p63 did not expressed in HCCs. Conclusion: Methylation status of p16(INK4 alpha) gene will play a part for reducing constitutive expression of p16(INK4 alpha) and of p21(wa f1) coordinately in HCCs. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.