Correlation between p21 waf1 and p16 INK4a expression in hepatocellular carcinoma

Abstract

Background: The cyclin dependent kinase p21 waf1 plays a crucial role in the regulation of cell cycle. The family of p53 proteins has the ability to induce p21 waf1, whereas p16 INK4a modulates post-transcriptionally the expression of p21 waf1. Methods: Total 36 hepatocellular carcinomas (HCCs) and 24 paired adjacent liver tissues were evaluated for the following: (1) expression of p21 waf1 and p16 INK4a ; (2) that of p21 waf1, p73 and p63 mRNAs; (3) genomic mutations and the loss of heterozygosity of p73 and p53; and (4) frequency of methylation in the 5′CpG promoter region of p16 INK4a . Results: In HCCs compared with the adjacent non-cancerous liver tissues, the expression of p21 waf1 and p16 INK4a 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 INK4a expression in all of them. p21 waf1 and p16 INK4a were reduced in proportion to the degree of methylation in p16 INK4a gene. p73 did not mutated, and p63 did not expressed in HCCs. Conclusion: Methylation status of p16 INK4a gene will play a part for reducing constitutive expression of p16 INK4a and of p21 waf1 coordinately in HCCs.