Knock down of hSNF5/Ini1 causes cell cycle arrest and apoptosis in a p53-dependent manner

Hiroyuki Kato, Reiko Honma, Takaomi Sanda, Toshiyoshi Fujiwara, Emi Ito, Yuka Yanagisawa, Jun ichi Imai, Takashi Okamoto, Shinya Watanabe

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

hSNF5/Ini1 is a core component of the SWI/SNF complex and the gene is frequently mutated in aggressive pediatric rhabdoid tumors. Mechanisms of the malignant transformation, however, remain poorly understood. We analyzed HeLa cells treated with siRNA to the hSNF5/Ini1 mRNA. The resulting efficient and long-term suppression caused characteristic cell enlargement, cell cycle arrest in G1 phase, and subsequent modest apoptosis. Gene expression profiling of the hSNF5-down-regulated cells by cDNA microarray analysis revealed that a limited number of p53-responsive genes, especially p21, were up-regulated. The p53 protein level was also greatly enhanced, suggesting that loss of hSNF5/Ini1 induces a p53 signaling pathway irrelevant to the chk1/2 phosphorylation pathway. Some rhabdoid tumors with very low or no ARF expression were induced to undergo cell enlargement, growth arrest, and, in one case, apoptosis by ectopic expression of the p14ARF protein. These results may in part account for molecular mechanisms of rhabdoid tumor formation.

Original languageEnglish
Pages (from-to)580-585
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume361
Issue number3
DOIs
Publication statusPublished - Sep 28 2007

Keywords

  • ARF
  • Apoptosis
  • G1 arrest
  • Rhabdoid tumor
  • hSNF5/Ini1
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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