| セッション情報 |
ポスターセッション(消化器病学会)
胆道（症例報告/その他）
|
| タイトル |
消P-157：Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells
|
| 演者 |
A. Gui（First Department of Surgery, Shinshu University School of Medicine） |
| 共同演者 |
A. Kobayashi（First Department of Surgery, Shinshu University School of Medicine）, H. Motoyama（First Department of Surgery, Shinshu University School of Medicine）, M. Kitazawa（First Department of Surgery, Shinshu University School of Medicine）, M. Takeoka（First Department of Surgery, Shinshu University School of Medicine）, S. Miyagawa（First Department of Surgery, Shinshu University School of Medicine） |
| 抄録 |
Objective: The present study sought to understand the molecular genetic characteristics of cholangiocarcinoma related to EGFR in order to develop more effective EGFR target treatments. Methods: We evaluated EGFR expression and colocalization by immunoblotting and immunofluorescence, cell surface EGFR expression by fluorescence-activated cell sorting (FACS), and EGFR ubiquitination and protein binding by immunoprecipitation in the human cholangiocarcinoma cell line RBE and immortalized cholangiocytes MMNK-1. Results: Upon stimulation with EGF, ligand-induced EGFR degradation was impaired and the expression of phospho-tyrosine 1068 and phospho-p44/42 MAPK was sustained in RBE cells as compared with MMNK-1 cells. In RBE cells, the process of EGFR sorting for lysosomal degradation was blocked at the early endosome stage, and non-degradated EGFR was recycled to the cell surface. A disrupted association between EGFR and the E3 ubiquitin ligase c-Cbl, as well as hypo-phosphorylation of EGFR at tyrosine 1045 (Tyr1045), was also observed in RBE cells. Conclusion: In RBE cells, up-regulation of EGFR Tyr1045 phosphorylation is a potentially useful molecular alteration in EGFR-targeted therapy. The combination of molecular targeted therapy determined by the characteristics of individual EGFR phosphorylation events and EGFR recycling inhibition show promise in future treatments of some types of cholangiocarcinoma. |
| 索引用語 |
Cholangiocarcinoma, Target |
