title: HGF increases cisplatin resistance via down-regulation of AIF in lung cancer cells.
abstract: Our previous study had shown that advanced stages of lung adenocarcinomas (ADC) was frequently associated with overexpression of hepatocyte growth factor (HGF), which has multipotent and anti-apoptotic activities. In this study, we examined the effect of HGF on gene expression of apoptosis-inducing factor (AIF) and cisplatin sensitivity in lung ADC cells. Expression of AIF was determined by immunocytochemistry and confocal immunofluorescence microscopy. Our data show that addition of HGF suppressed AIF expression and increased cisplatin resistance. The effect could be through HGF receptor and its downstream effector, focal adhesion kinase (FAK). Interestingly, knockout of FAK gene increased AIF expression and drug sensitivity. Re-introduction of FAK gene, on the other hand, restored drug resistance. These results suggested that HGF might induce cisplatin resistance via c-Met to activate FAK and down-regulate AIF expression.
authors: Graduate Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung, 40227 Taiwan.
authors: Jin-Tang
authors: JT
authors: Chen
authors: Chih-Yang
authors: CY
authors: Huang
authors: Yung-Yen
authors: YY
authors: Chiang
authors: Wen-Heng
authors: WH
authors: Chen
authors: Shiow-Her
authors: SH
authors: Chiou
authors: Chih-Yi
authors: CY
authors: Chen
authors: Kuan-Chih
authors: KC
authors: Chow
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051033:Apoptosis Inducing Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology
chemical_list: C494829:AIFM1 protein, human; D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D002945:Cisplatin