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

Fingerprint

Rhabdoid Tumor
Cell Cycle Checkpoints
Cell Enlargement
Tumors
Cells
Apoptosis
Genes
Tumor Suppressor Protein p14ARF
Tissue Array Analysis
Phosphorylation
Pediatrics
p53 Genes
G1 Phase
Cell growth
Gene Expression Profiling
Microarrays
Oligonucleotide Array Sequence Analysis
HeLa Cells
Gene expression
Small Interfering RNA

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Knock down of hSNF5/Ini1 causes cell cycle arrest and apoptosis in a p53-dependent manner. / Kato, Hiroyuki; Honma, Reiko; Sanda, Takaomi; Fujiwara, Toshiyoshi; Ito, Emi; Yanagisawa, Yuka; Imai, Jun ichi; Okamoto, Takashi; Watanabe, Shinya.

In: Biochemical and Biophysical Research Communications, Vol. 361, No. 3, 28.09.2007, p. 580-585.

Research output: Contribution to journalArticle

Kato, Hiroyuki ; Honma, Reiko ; Sanda, Takaomi ; Fujiwara, Toshiyoshi ; Ito, Emi ; Yanagisawa, Yuka ; Imai, Jun ichi ; Okamoto, Takashi ; Watanabe, Shinya. / Knock down of hSNF5/Ini1 causes cell cycle arrest and apoptosis in a p53-dependent manner. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 361, No. 3. pp. 580-585.
@article{4740a84f125b4a04b878ba2473009cd3,
title = "Knock down of hSNF5/Ini1 causes cell cycle arrest and apoptosis in a p53-dependent manner",
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.",
keywords = "Apoptosis, ARF, G1 arrest, hSNF5/Ini1, p53, Rhabdoid tumor",
author = "Hiroyuki Kato and Reiko Honma and Takaomi Sanda and Toshiyoshi Fujiwara and Emi Ito and Yuka Yanagisawa and Imai, {Jun ichi} and Takashi Okamoto and Shinya Watanabe",
year = "2007",
month = "9",
day = "28",
doi = "10.1016/j.bbrc.2007.07.035",
language = "English",
volume = "361",
pages = "580--585",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Knock down of hSNF5/Ini1 causes cell cycle arrest and apoptosis in a p53-dependent manner

AU - Kato, Hiroyuki

AU - Honma, Reiko

AU - Sanda, Takaomi

AU - Fujiwara, Toshiyoshi

AU - Ito, Emi

AU - Yanagisawa, Yuka

AU - Imai, Jun ichi

AU - Okamoto, Takashi

AU - Watanabe, Shinya

PY - 2007/9/28

Y1 - 2007/9/28

N2 - 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.

AB - 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.

KW - Apoptosis

KW - ARF

KW - G1 arrest

KW - hSNF5/Ini1

KW - p53

KW - Rhabdoid tumor

UR - http://www.scopus.com/inward/record.url?scp=34547819250&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547819250&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2007.07.035

DO - 10.1016/j.bbrc.2007.07.035

M3 - Article

C2 - 17669367

AN - SCOPUS:34547819250

VL - 361

SP - 580

EP - 585

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -