Decreased expression of the SIN3A gene, a candidate tumor suppressor located at the prevalent allelic loss region 15q23 in non-small cell lung cancer.
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.
Suzuki
Hiromitsu
H
Department of Surgical Oncology and Thoracic Surgery, Okayama University, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
Ouchida
Mamoru
M
Yamamoto
Hiromasa
H
Yano
Masaaki
M
Toyooka
Shinichi
S
Aoe
Motoi
M
Shimizu
Nobuyoshi
N
Date
Hiroshi
H
Shimizu
Kenji
K
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics*; D056264:Sin3 Histone Deacetylase and Corepressor Complex
D012097:Repressor Proteins; C099683:SIN3A transcription factor; D056264:Sin3 Histone Deacetylase and Corepressor Complex