Department , Position
|Title||Inhibition of mammalian target of rapamycin(mTOR)signaling by Temsirolimus as a potential therapeutic strategy for esophageal cancer treatment.|
|Conference||American Association for Cancer Reserch 102nd ANNUAL MEETING|
|Conference Type||International society and overseas society|
|Presentation Type||Poster notice|
|Publisher and common publisher||◎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|
(city and name of the country)
|Summary||[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.