Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer

Chiang,Yung-Yen; Chow,Kuan-Chih; Lin,Tze-Yi; Chiang,I-Ping; Fang,Hsing-Yuan

doi:10.3892/or.2013.2867

Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer

Authors:
- Yung-Yen Chiang
- Kuan-Chih Chow
- Tze-Yi Lin
- I-Ping Chiang
- Hsing-Yuan Fang
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Affiliations: Department of Dental Laboratory Technology, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C., Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, R.O.C., Department of Pathology, China Medical University Hospital, Taichung, Taiwan, R.O.C., Department of Surgery, China Medical University Hospital, Taichung, Taiwan, R.O.C.
Published online on: November 25, 2013 https://doi.org/10.3892/or.2013.2867
Pages: 597-604

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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.

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