Decreased expression of the SIN3A gene, a candidate tumor suppressor located at the prevalent allelic loss region 15q23 in non-small cell lung cancer

Hiromitsu Suzuki, Mamoru Oouchida, Hiromasa Yamamoto, Masaaki Yano, Shinichi Toyooka, Motoi Aoe, Nobuyoshi Shimizu, Hiroshi Date, Kenji Shimizu

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

To identify the tumor suppressor genes (TSG) associated with non-small cell lung cancers (NSCLC), we performed the loss of heterozygosity (LOH) analysis in NSCLC samples from 66 patients. We focused on the novel hot spot region on 15q14-24 with eight polymorphic microsatellite markers. Frequent allelic loss was detected in 33 of 48 informative cases (69%) at D15S984 on 15q23. We defined the fine map on the region and identified the SIN3A gene as a candidate TSG. The SIN3A gene product is a component of the histone deacetylase (HDAC) complex and plays essential roles in early embryonic development and the proliferation and survival of a variety of cells through the repression of diverse signaling pathways. Our expression analysis revealed more frequent down-regulation of the SIN3A mRNA in 19 of 31 cases (61%) of NSCLCs in comparison to those of other flanking genes (16-42%), albeit the correlation of the decreased expression with the LOH did not attain statistic significance. These results suggest that the attenuated function of SIN3A due to a decreased level of expression may result in epigenetic de-regulation of growth-related genes through histone acetylation, which leads to the tumorigenesis of lung cancer cells. To our knowledge, this is the first evidence of the down-regulation of the SIN3A gene in human cancer.

Original languageEnglish
Pages (from-to)24-31
Number of pages8
JournalLung Cancer
Volume59
Issue number1
DOIs
Publication statusPublished - Jan 2008

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Loss of Heterozygosity
Non-Small Cell Lung Carcinoma
Gene Expression
Genes
Neoplasms
Tumor Suppressor Genes
Down-Regulation
Histone Deacetylases
Acetylation
Epigenomics
Microsatellite Repeats
Histones
Embryonic Development
Lung Neoplasms
Carcinogenesis
Messenger RNA
Survival
Growth

Keywords

  • Chromosome 15
  • LOH
  • Lung cancer
  • SIN3A

ASJC Scopus subject areas

  • Oncology

Cite this

Decreased expression of the SIN3A gene, a candidate tumor suppressor located at the prevalent allelic loss region 15q23 in non-small cell lung cancer. / Suzuki, Hiromitsu; Oouchida, Mamoru; Yamamoto, Hiromasa; Yano, Masaaki; Toyooka, Shinichi; Aoe, Motoi; Shimizu, Nobuyoshi; Date, Hiroshi; Shimizu, Kenji.

In: Lung Cancer, Vol. 59, No. 1, 01.2008, p. 24-31.

Research output: Contribution to journalArticle

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abstract = "To identify the tumor suppressor genes (TSG) associated with non-small cell lung cancers (NSCLC), we performed the loss of heterozygosity (LOH) analysis in NSCLC samples from 66 patients. We focused on the novel hot spot region on 15q14-24 with eight polymorphic microsatellite markers. Frequent allelic loss was detected in 33 of 48 informative cases (69{\%}) at D15S984 on 15q23. We defined the fine map on the region and identified the SIN3A gene as a candidate TSG. The SIN3A gene product is a component of the histone deacetylase (HDAC) complex and plays essential roles in early embryonic development and the proliferation and survival of a variety of cells through the repression of diverse signaling pathways. Our expression analysis revealed more frequent down-regulation of the SIN3A mRNA in 19 of 31 cases (61{\%}) of NSCLCs in comparison to those of other flanking genes (16-42{\%}), albeit the correlation of the decreased expression with the LOH did not attain statistic significance. These results suggest that the attenuated function of SIN3A due to a decreased level of expression may result in epigenetic de-regulation of growth-related genes through histone acetylation, which leads to the tumorigenesis of lung cancer cells. To our knowledge, this is the first evidence of the down-regulation of the SIN3A gene in human cancer.",
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