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

Citation
K. Fukushima et al., Correlation between p21(waf1) and p16(INK4 alpha) expression in hepatocellular carcinoma, HEPATOL RES, 20(1), 2001, pp. 52-67
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology
Journal title
HEPATOLOGY RESEARCH
ISSN journal
1386-6346 → ACNP
Volume
20
Issue
1
Year of publication
2001
Pages
52 - 67
Database
ISI
SICI code
1386-6346(200105)20:1<52:CBPAPA>2.0.ZU;2-N
Abstract
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.