| RRC ID |
43668
|
| 著者 |
Tseng PC, Huang WC, Chen CL, Sheu BS, Shan YS, Tsai CC, Wang CY, Chen SO, Hsieh CY, Lin CF.
|
| タイトル |
Regulation of SHP2 by PTEN/AKT/GSK-3β signaling facilitates IFN-γ resistance in hyperproliferating gastric cancer.
|
| ジャーナル |
Immunobiology
|
| Abstract |
Oncogenic activation accompanied by escape from immune surveillance, such as IFN-γ resistance, is critical for cancer cell growth and survival. In this study, we investigated the crosstalk signaling between IFN-γ resistance and signaling of hyperproliferation in gastric cancer cells. IFN-γ inhibited the cell growth of MKN45 cells but not hyperproliferating AGS cells. AGS cells did not respond to IFN-γ because of a decrease in STAT1 but not due to dysfunctional IFN-γ receptors. Signaling of PI3K/AKT, as well as MEK/ERK, was required for the hyperproliferation; notably, PI3K/AKT alone mediated the IFN-γ resistance. Aberrant Src homology-2 domain-containing phosphatase (SHP) 2 determined IFN-γ resistance but unexpectedly had no effects on hyperproliferation or ERK activation. In the IFN-γ resistant cells, inactivation of glycogen synthase kinase (GSK)-3β by PI3K/AKT was important for SHP2 activation but not for hyperproliferation. An imbalance of AKT/GSK-3β/SHP2 caused by a reduction of PTEN was important for the crosstalk between IFN-γ resistance and hyperproliferation. PI3K is constitutively expressed in AGS cells and immunohistochemical staining showed a correlation between hyperproliferation and expression of SHP2 and STAT1 in gastric tumors. These results demonstrate the effects of PTEN/AKT/GSK-3β/SHP2 signaling on IFN-γ resistance in hyperproliferating gastric cancer cells.
|
| 巻・号 |
217(9)
|
| ページ |
926-34
|
| 公開日 |
2012-9-1
|
| DOI |
10.1016/j.imbio.2012.01.001
|
| PII |
S0171-2985(12)00004-6
|
| PMID |
22325465
|
| MeSH |
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Resistance, Neoplasm*
Enzyme Activation
Glycogen Synthase Kinase 3 / metabolism*
Glycogen Synthase Kinase 3 beta
Humans
Interferon-gamma / pharmacology*
Mitogen-Activated Protein Kinases / metabolism
PTEN Phosphohydrolase / metabolism*
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
STAT1 Transcription Factor / metabolism
Signal Transduction / drug effects
Stomach Neoplasms / metabolism*
|
| IF |
2.788
|
| 引用数 |
26
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
