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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Alteration of the p14(ARF) gene and p53 status in human hepatocellular carcinomas

Teruaki Ito1, Naoshi Nishida, Yoshihiro Fukuda

  • 1Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.

Journal of Gastroenterology
|May 29, 2004
PubMed
Abstract

Insights

Alterations in the p14ARF gene are infrequent in Japanese hepatocellular carcinoma (HCC) but may contribute to early tumor development. Overexpression of p14ARF is common, particularly in poorly differentiated HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The INK4a/ARF locus encodes tumor suppressors p16INK4a and p14ARF, critical for cell cycle regulation.
  • While RB/p16INK4a pathway alterations are common in hepatocellular carcinoma (HCC), p14ARF gene alterations in Japanese HCC remain under-investigated.

Purpose of the Study:

  • To investigate the role of p53/ARF pathway alterations in hepatocarcinogenesis.
  • To analyze p14ARF gene alterations (mRNA expression, deletion, mutation, methylation) and p53 alterations in Japanese HCC.

Main Methods:

  • Analysis of 44 HCC samples for p14ARF mRNA expression, deletion, mutation, and promoter hypermethylation.
  • Simultaneous analysis of p53 alterations in the same HCC cohort.
  • Immunohistochemistry and TaqMan PCR were employed for expression and alteration analysis.

Main Results:

  • p14ARF alterations (homozygous deletion, mutation) were found in 3/44 HCCs, predominantly well-differentiated.
  • p53 alterations were observed in 12/44 HCCs, with only one being well-differentiated.
  • p14ARF expression was significantly higher in HCC than non-tumorous tissues (P < 0.0001), correlating with poor differentiation.

Conclusions:

  • p14ARF alterations are infrequent in Japanese HCC but may play a role in early hepatocarcinogenesis.
  • Overexpression of p14ARF is frequently observed in HCC, especially in poorly differentiated tumors, suggesting a response to oncogenic stimuli.
  • The study highlights the distinct roles of p14ARF and p53 alterations in HCC development.

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