| RRC ID |
62990
|
| 著者 |
Sakuratani T, Takeuchi T, Yasufuku I, Iwata Y, Saigo C, Kito Y, Yoshida K.
|
| タイトル |
Downregulation of ARID1A in gastric cancer cells: a putative protective molecular mechanism against the Harakiri-mediated apoptosis pathway.
|
| ジャーナル |
Virchows Arch
|
| Abstract |
This study was designed to unravel the pathobiological role of impaired ARID1A expression in gastric carcinogenesis. We examined ARID1A expression immunohistochemically in 98 gastric cancer tissue specimens with regard to the clinicopathological features. Based on the proportion and intensity of ARID1A immunoreactivity at the cancer invasion front, we subdivided the specimens into low- and high-expression ARID1A groups. Notably, low ARID1A expression was significantly correlated with overall survival of the patients. Subsequently, we determined the molecular signature that distinguished ARID1A low/poor prognosis from ARID1A high/good prognosis gastric cancers. A comprehensive gene profiling analysis followed by immunoblotting revealed that a mitochondrial apoptosis mediator, Harakiri, was less expressed in ARID1A low/poor prognosis than ARID1A high/good prognosis gastric cancers. siRNA-mediated ARID1A downregulation significantly reduced expression of the Harakiri molecule in cultured gastric cancer cells. Interestingly, downregulation of ARID1A conferred resistance to apoptosis induced by the mitochondrial metabolism inhibitor, devimistat. In contrast, enforced Harakiri expression restored sensitivity to devimistat-induced apoptosis in ARID1A downregulated gastric cancer cells. The present findings indicate that impaired ARID1A expression might lead to gastric carcinogenesis, putatively through gaining resistance to the Harakiri-mediated apoptosis pathway.
|
| 巻・号 |
478(3)
|
| ページ |
401-411
|
| 公開日 |
2021-3-1
|
| DOI |
10.1007/s00428-020-02899-1
|
| PII |
10.1007/s00428-020-02899-1
|
| PMID |
32789692
|
| MeSH |
Adult
Aged
Aged, 80 and over
Antineoplastic Agents / pharmacology
Apoptosis* / drug effects
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism*
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Caprylates / pharmacology
Cell Line, Tumor
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Prognosis
Retrospective Studies
Signal Transduction
Stomach Neoplasms / drug therapy
Stomach Neoplasms / genetics
Stomach Neoplasms / metabolism*
Stomach Neoplasms / pathology
Sulfides / pharmacology
Transcription Factors / genetics
Transcription Factors / metabolism*
|
| IF |
2.906
|
| リソース情報 |
| ヒト・動物細胞 |
NUGC-4(RCB1939)
MKN74(RCB1002) |
