モリタ　イチロウ   Ichiro Morita   森田　一郎    所属   川崎医科大学  医学部 臨床医学　総合外科学    職種   特任教授
言語種別	英語
発表タイトル	Inhibition of mammalian target of rapamycin(mTOR)signaling by Temsirolimus as a potential therapeutic strategy for esophageal cancer treatment.
会議名	American Association for Cancer Reserch 102nd ANNUAL MEETING
学会区分	国際学会及び海外の学会
発表形式	ポスター掲示
発表者・共同発表者	◎Munenori Takaoka, Toshio Nishikawa, Toshiaki Ohara, Yasuko Tomono, Yasuhiro Fujiwara, Yasuhiro Shirakawa, Hitoshi Nagatsuka, Takuya Fukazawa, Tomoki Yamatsuji, Xiaohong Bao, Huifang Hao, Kaori Shigemitsu, Ichiro Morita, Toshiyoshi Fujiwara, Yoshio Naomoto
発表年月日	2011/04/04
開催地 （都市, 国名）	Florida,USA
概要	[Background] Heat shock protein90(HSP90) has provoked great interest as a promising molecular target for cancer treatment, since it is involved in regulating the conformation, stability and functions of key oncogenic proteins. [Materials and Methods]esophageal cancer cells(TE-1, TE-4, TE-8, TE-10), Gastric cancer cells(NUGC-3, NUGC-3/IL), pancreatic cancer cells(PANC-1, MIAPACA-2, Bxpc3) and mutant c-kit-driven lymphocytes(Ba/F3-Kofi, Ba/F3-K642, Ba/F3-820Mz), mimicking gastrointestinal stromal tumor cells, were examined. WST assay was conducted to assess the anti-proliferation effects of NVP-AUY922. The activity of cell growth-related molecules were investigated by western blot Genetic modification using siRNA and expression vector were applied for silencing and overexpression of PTEN, respectively. [Results]NVP-AUY922 potently inhibits the proliferation of human cancer cell lines, regardless of 5-FU resistance or c-Kit mutation, by which the sensitivity to imatinib can be affected. PTEN-null TE-4 cells exhibited more sensitivity to NVP-AUY922. The sensitivity to NVP-AUY922 was increased by silencing PTEN expression in intact PTEN expressing TE-10 cells and decreased by exogenous transduction of PTEN in TE-4 cells. Furthermore, NVP-AUY922 significantly inhibited the activity of AKT and ERK in TE-4 cells, but not in TE-10 cells. [Conclusion]NVP-AUY922 exhibited strong cytotoxicity against most of the cancer cells, including some anticancer drug-resistant cells. The expression status of PTEN determines the sensitivity to HSP90 inhibitor.