title: Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer.
abstract: Our previous study showed that patients with advanced stages of non-small cell lung cancer (NSCLC) were frequently detected with upregulation of hepatocyte growth factor (HGF). In vitro, HGF reduced expression of apoptosis-inducing factor (AIF) and cisplatin sensitivity in NSCLC cells. The effect of HGF was via HGF receptor (c-MET) and the downstream effector, focal adhesion kinase (FAK). In this study, we determined the prognostic value of AIF in NSCLC patients. AIF expression was determined by immunohistochemistry and immunoblotting. Our data show that AIF expression was associated with better prognosis. Expression of AIF inversely correlated with that of positive NSCLC markers, e.g., dihydrodiol dehydrogenase (DDH), c-MET, short oncostatin M receptor (OSMRs), matrix metalloproteinase (MMP)-1, and HER2/neu, which were closely associated with drug resistance, tumor recurrence, metastasis and poor prognosis. Noteworthy, silence of HER2/neu gene expression increases AIF level and drug sensitivity. Addition of HGF inhibits AIF expression in HER2/neu-silenced cells. These results suggested that both HGF and HER2/neu affect drug resistance by regulating AIF expression in NSCLC.
authors.affiliation: Department of Dental Laboratory Technology, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.
authors.forename: Yung-Yen
authors.initials: YY
authors.lastname: Chiang
authors.affiliation: Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, R.O.C.
authors.forename: Kuan-Chih
authors.initials: KC
authors.lastname: Chow
authors.affiliation: Department of Pathology, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Tze-Yi
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Department of Pathology, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: I-Ping
authors.initials: IP
authors.lastname: Chiang
authors.affiliation: Department of Surgery, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Hsing-Yuan
authors.initials: HY
authors.lastname: Fang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D000071877:Checkpoint Kinase 1; D002945:Cisplatin / Q000494:pharmacology; D018572:Disease-Free Survival; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis; D053681:Oncostatin M Receptor beta Subunit / Q000096:biosynthesis; D010088:Oxidoreductases / Q000096:biosynthesis; D011494:Protein Kinases / Q000096:biosynthesis; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D012907:Smoking; D013534:Survival; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D002945:Cisplatin; D051417:Focal Adhesion Kinase 1; D017228:Hepatocyte Growth Factor; D020781:Matrix Metalloproteinase 1; D009687:Nuclear Proteins; D053681:Oncostatin M Receptor beta Subunit; D010088:Oxidoreductases; D011494:Protein Kinases; D019859:Proto-Oncogene Proteins c-met; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; C112156:NBN protein, human; C508348:OSMR protein, human; C048338:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; C508053:ERBB2 protein, human; C491743:MET protein, human; C496050:PTK2 protein, human; C522360:MMP1 protein, human