title: Hepatocyte growth factor promotes cell survival by phosphorylation of BAD in gastric cancer cells.
abstract: 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.
authors.affiliation: Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu, Korea. lkhee@med.yu.ac.kr
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Lee
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Myung Soo
authors.initials: MS
authors.lastname: Hyun
authors.forename: Jong Ryul
authors.initials: JR
authors.lastname: Eun
authors.forename: Byung Ik
authors.initials: BI
authors.lastname: Jang
authors.forename: Tae Nyeun
authors.initials: TN
authors.lastname: Kim
authors.forename: Sang Woon
authors.initials: SW
authors.lastname: Kim
authors.forename: Sun Kyo
authors.initials: SK
authors.lastname: Song
authors.forename: Jung Hye
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae-Ryong
authors.initials: JR
authors.lastname: Kim
mesh_terms: 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*
chemical_list: 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