論文 - 詳細
| RRC ID | 61492 |
|---|---|
| 著者 | Tominaga K, Higuchi K, Sasaki E, Suto R, Watanabe T, Fujiwara Y, Oshitani N, Matsumoto T, Kim S, Iwao H, Arakawa T. |
| タイトル | Correlation of MAP kinases with COX-2 induction differs between MKN45 and HT29 cells. |
| ジャーナル | Aliment Pharmacol Ther |
| Abstract |
BACKGROUND:Mitogen-activated protein (MAP) kinases, including extracellular signal-regulated kinases (ERK),c-Jun NH2-terminal kinases (JNK) and p38 MAP kinase (p38 MAPK) are important intermediates of the signal-transduction pathway from the cell surface to the nucleus. Expression of cyclooxygenase (COX)-2, associated with proliferation, apoptosis or both of gastrointestinal cancer cells, is mediated through MAP kinase families. However, the correlation between respective MAP kinase signals and COX-2 in the proliferation of gastric and colon cancer cells has not been well elucidated. AIM:We examined the effect of selective inhibitors of MAP kinases and COX-2 on serum-induced proliferation of gastric (MKN45) and colon (HT29) cancer cells. METHODS:After 24-h serum starvation, cancer cells were stimulated with 2% serum and COX-2 inhibitors (NS398 10 micromol/L, or etodolac 100 micromol/L) or 1 h after preincubation with inhibitors for ERK (PD98059 20 micromol/L) or p38 MAPK (SB203580 10 micromol/L). Phosphorylated MAP kinases and COX-2 protein were evaluated by Western blotting, and the proliferation of cancer cells was estimated by 3H-thymidine incorporation. Transcription factors nuclear factor-kappaB and CREB were assayed by an electorophoretic mobility shift assay. RESULTS:Serum increased the proliferation of MKN45 and HT29 cells by 280% and 200%, respectively, compared with the control levels (100%). In both cancer cells, phosphorylated MAP kinases were increased within 30 min after stimulation. PD98059 and SB203580 inhibited the serum-induced proliferation of MKN45 by 21% and 51% and of HT29 by 81% and 69%, respectively. NS398 and etodolac inhibited the proliferation of HT29 by 21% and 41%, respectively, but not that of MKN45. PD98059 and SB203580 also suppressed serum-induced expression of COX-2 protein in HT29 cells. In addition to the activation of MAP kinases and COX-2, activities of nuclear factor-kappaB and CREB were also increased during HT29 cell proliferation. CONCLUSIONS:These results suggest that the correlation of MAP kinases with COX-2 induction for cell proliferation differs between MKN45 and HT29 cells. |
| 巻・号 | 20 Suppl 1 |
| ページ | 143-50 |
| 公開日 | 2004-7-1 |
| DOI | 10.1111/j.1365-2036.2004.01986.x |
| PII | APT1986 |
| PMID | 15298620 |
| MeSH | Blotting, Western Cell Division Cell Line, Tumor Colonic Neoplasms / enzymology* Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors / pharmacology Enzyme Inhibitors / pharmacology Flavonoids / pharmacology HT29 Cells Humans Imidazoles / pharmacology Isoenzymes / antagonists & inhibitors Isoenzymes / metabolism* Membrane Proteins Mitogen-Activated Protein Kinase Kinases / metabolism* Prostaglandin-Endoperoxide Synthases / metabolism* Pyridines / pharmacology Serum / physiology Stomach Neoplasms / enzymology* |
| IF | 7.515 |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |