| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2013-03-26 |
| タイトル |
|
|
タイトル |
Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells |
| 言語 |
|
|
言語 |
eng |
| DOI |
|
|
|
関連識別子 |
https://doi.org/10.1186/1471-2407-12-179 |
|
|
関連名称 |
10.1186/1471-2407-12-179 |
| キーワード |
|
|
主題 |
Cholangiocarcinoma, RBE cells, EGFR, Tyrosine 1045, Down-regulation, Recycling, Target |
| 資源タイプ |
|
|
資源 |
http://purl.org/coar/resource_type/c_6501 |
|
タイプ |
journal article |
| 著者 |
Gui, Anping
Kobayashi, Akira
Motoyama, Hiroaki
Kitazawa, Masato
Takeoka, Michiko
Miyagawa, Shinichi
|
| 出版者 |
|
|
出版者 |
BIOMED CENTRAL LTD |
| 引用 |
|
|
内容記述 |
BMC Cancer. 2012, 12:179 |
| 書誌情報 |
BMC CANCER
巻 12,
号 AA12034763,
発行日 2012-05-16
|
| 内容記述 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
信州大学博士（医学）・学位論文・平成24年6月11日授与（甲第929号）・桂安萍 |
| 抄録 |
|
|
内容記述 |
Background: Since cholangiocarcinoma has a poor prognosis, several epidermal growth factor receptor (EGFR)-targeted therapies with antibody or small molecule inhibitor treatment have been proposed. However, their effect remains limited. The present study sought to understand the molecular genetic characteristics of cholangiocarcinoma related to EGFR, with emphasis on its degradation and recycling. 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 RBE and immortalized cholangiocyte MMNK-1 cell lines. Monensin treatment and Rab11a depletion by siRNA were adopted for inhibition of EGFR recycling. 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), were 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 cholangiocarcinoma. |
| 資源タイプ（コンテンツの種類） |
|
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1471-2407 |
| 書誌レコードID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12034763 |
| PubMed |
|
|
|
識別子タイプ |
PMID |
|
|
関連識別子 |
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=22591401 |
|
|
関連名称 |
22591401 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| WoS |
|
|
URL |
http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000310059500001 |
H24Kou929_Gui.pdf (1.9 MB)
