| RRC ID |
36890
|
| 著者 |
Saeki N, Ono H, Yanagihara K, Aoyagi K, Sasaki H, Sakamoto H, Yoshida T.
|
| タイトル |
rs2294008T, a risk allele for gastric and gallbladder cancers, suppresses the PSCA promoter by recruiting the transcription factor YY1.
|
| ジャーナル |
Genes Cells
|
| Abstract |
Previous genomewide association studies identified prostate stem cell antigen (PSCA) as a gastric cancer (GC) susceptibility gene and showed an association between GC and the T allele of the single nucleotide polymorphism rs2294008 (C/T) in this gene. The protein product of this gene inhibits cell growth, and the T allele significantly suppresses the transcriptional activity of the -3.2 kb PSCA upstream region. However, the mechanism remains unknown. In this study, we conducted reporter assays using the PSCA upstream region containing the C allele and identified the region from -200 to +38 bp of the transcription initiation site of the gene as a critical region of the -3.2 kb PSCA upstream region. We found that introducing the T allele at rs2294008 generated a consensus binding sequence for the Polycomb group transcription factor Yin Yang 1 (YY1) and that disruption of the consensus sequence restored the transcriptional activity to the -3.2 kb PSCA upstream region. These findings imply that the T allele significantly suppresses PSCA expression in vivo by recruiting YY1 to its promoter, which eventually predisposes gastric epithelial cells to GC development.
|
| 巻・号 |
20(5)
|
| ページ |
382-91
|
| 公開日 |
2015-5-1
|
| DOI |
10.1111/gtc.12228
|
| PMID |
25727947
|
| MeSH |
Alleles*
Antigens, Neoplasm / genetics*
Base Sequence
Binding Sites
Consensus Sequence
GPI-Linked Proteins / genetics
Gallbladder Neoplasms / genetics*
Gallbladder Neoplasms / metabolism*
Gastric Mucosa / metabolism
Gastric Mucosa / pathology
Gene Expression Regulation, Neoplastic*
Gene Order
Humans
Molecular Sequence Data
Neoplasm Proteins / genetics*
Promoter Regions, Genetic*
Protein Binding
Stomach Neoplasms / genetics*
Stomach Neoplasms / metabolism*
Transcription, Genetic
YY1 Transcription Factor / metabolism*
|
| IF |
1.655
|
| 引用数 |
10
|
|
WOS 分野
|
GENETICS & HEREDITY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
TGBC1TKB(RCB1129) |
