論文 - 詳細
| RRC ID | 37686 |
|---|---|
| 著者 | Seto M, Ohta M, Asaoka Y, Ikenoue T, Tada M, Miyabayashi K, Mohri D, Tanaka Y, Ijichi H, Tateishi K, Kanai F, Kawabe T, Omata M. |
| タイトル | Regulation of the hedgehog signaling by the mitogen-activated protein kinase cascade in gastric cancer. |
| ジャーナル | Mol Carcinog |
| Abstract |
The hedgehog and mitogen-activated protein kinase (MAPK) signaling pathways regulate growth in many tumors, suggesting cooperation between these two pathways in the regulation of cell proliferation. However, interactions between these pathways have not been extensively studied. We assessed cross-talk between hedgehog and MAPK signaling in the regulation of cell proliferation in gastric cancer. We showed that PTCH expression was significantly correlated with extracellular signal-regulated kinase (ERK) 1/2 phosphorylation (P = 0.016) as well as SHH expression (P = 0.034) in the 35 gastric cancers assessed by immunohistochemistry. Indeed, MAPK signaling increased the GLI transcriptional activity and induced the expression of hedgehog target genes in gastric cancer cells. The inductive effect of activated KRAS and mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1 was blocked by the suppressor of fused (SUFU), indicating that MAPK signaling regulates GLI activity via a SUFU-independent process. Moreover, the deletion of the NH2-terminal domain of GLI1 gene resulted in reduced response to MEK1 stimulation. Our results suggest that the KRAS-MEK-ERK cascade has a positive regulatory role in GLI transcriptional activity in gastric cancer. |
| 巻・号 | 48(8) |
| ページ | 703-12 |
| 公開日 | 2009-8-1 |
| DOI | 10.1002/mc.20516 |
| PMID | 19142899 |
| MeSH | Adenocarcinoma, Mucinous / genetics Adenocarcinoma, Mucinous / metabolism Adenocarcinoma, Mucinous / pathology Adult Aged Aged, 80 and over Blotting, Western Carcinoma, Papillary / genetics Carcinoma, Papillary / metabolism Carcinoma, Papillary / pathology ErbB Receptors / genetics Female Gene Amplification Hedgehog Proteins / metabolism Humans Immunoenzyme Techniques JNK Mitogen-Activated Protein Kinases / metabolism Male Middle Aged Mitogen-Activated Protein Kinase 3 / metabolism Mitogen-Activated Protein Kinase Kinases / metabolism Mitogen-Activated Protein Kinases / metabolism* Patched Receptors Patched-1 Receptor Phosphorylation Proto-Oncogene Proteins c-jun / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, Cell Surface / genetics Receptors, Cell Surface / metabolism* Repressor Proteins / genetics Repressor Proteins / metabolism* Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / genetics Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Transcription Factors / genetics* Transcription Factors / metabolism Zinc Finger Protein GLI1 p38 Mitogen-Activated Protein Kinases / metabolism ras Proteins / metabolism |
| IF | 3.825 |
| 引用数 | 84 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |