Hepatocyte growth factor promotes cell survival by phosphorylation of BAD in gastric cancer cells.
Hepatocyte growth factor (HGF) is one of the survival factors with a potent ability to promote cell survival by inhibiting apoptosis. However, the mechanism by which HGF inhibits apoptosis is not completely understood. To explore the genes associated with stomach cancer cell survival by HGF, we used cDNA microarray technology and selected 26 genes up- or downregulated in NUGC-3 cells during HGF treatment. Among them, BAD was confirmed to be upregulated at the RNA and protein levels by HGF treatment. We investigated the effect of BAD induced by HGF on cell survival. HGF treatment inhibited apoptosis induced by BAD overexpression and enhanced BAD phosphorylation. Pretreatment of NUGC-3 cells with PI3K inhibitors, LY 294002, decreased HGF-induced BAD phosphorylation on Ser136 whereas an MEK inhibitor, PD 98059, decreased BAD phosphorylation on Ser112. In conclusion, increases in BAD levels as well as BAD phosphoryation by HGF might contribute to HGF-mediated cell survival in NUGC-3 cells.
Lee
Kyung Hee
KH
Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu, Korea. lkhee@med.yu.ac.kr
Choi
Eun Young
EY
Kim
Min Kyoung
MK
Hyun
Myung Soo
MS
Eun
Jong Ryul
JR
Jang
Byung Ik
BI
Kim
Tae Nyeun
TN
Kim
Sang Woon
SW
Song
Sun Kyo
SK
Kim
Jung Hye
JH
Kim
Jae-Ryong
JR
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D013274:Stomach Neoplasms / Q000473:pathology*; D051025:bcl-Associated Death Protein / Q000378:metabolism*
C494819:BAD protein, human; D051025:bcl-Associated Death Protein; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human