Epidermal growth factor receptor mutation enhances expression of vascular endothelial growth factor in lung cancer

Ming-Szu Hung; I-Chuan Chen; Paul-Yann Lin; Jr-Hau Lung; Ya-Chin Li; Yu-Ching Lin; Cheng-Ta Yang; Ying-Huang Tsai

doi:10.3892/ol.2016.5287

Epidermal growth factor receptor mutation enhances expression of vascular endothelial growth factor in lung cancer

Oncol Lett. 2016 Dec;12(6):4598-4604. doi: 10.3892/ol.2016.5287. Epub 2016 Oct 18.

Authors

Ming-Szu Hung¹, I-Chuan Chen², Paul-Yann Lin³, Jr-Hau Lung⁴, Ya-Chin Li⁴, Yu-Ching Lin¹, Cheng-Ta Yang⁵, Ying-Huang Tsai⁶

Affiliations

¹ Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Puzih, Chiayi 61363, Taiwan, R.O.C.; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, R.O.C.; Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi Campus, Puzih, Chiayi 61363, Taiwan, R.O.C.
² Department of Emergency Medicine, Chang Gung Memorial Hospital, Puzih, Chiayi 61363, Taiwan, R.O.C.
³ Department of Anatomic Pathology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan, R.O.C.
⁴ Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Puzih, Chiayi 61363, Taiwan, R.O.C.
⁵ Division of Pulmonary and Critical Care Medicine, Chang-Gung Memorial Hospital, Taoyuan 33305, Taiwan, R.O.C.; Department of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, R.O.C.
⁶ Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Puzih, Chiayi 61363, Taiwan, R.O.C.; Department of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, R.O.C.

Abstract

Epidermal growth factor receptor (EGFR) activation has been demonstrated to have a critical role in tumor angiogenesis. In the present study, the correlation between EGFR mutations and vascular endothelial growth factor (VEGF) was investigated in lung cancer cell lines and non-small-cell lung cancer (NSCLC) tumor tissues. VEGF levels were significantly increased in culture medium of lung cancer cells and NSCLC tissues with EGFR mutations (H1650 vs. A549, P=0.0399; H1975 vs. A549, P<0.0001). Stable lung cancer cell lines expressing mutant (exon 19 deletion, E746-A750; exon 21 missense mutation, L858R) and wild-type EGFR genes were established. Significantly increased expression of VEGF and stronger inhibitory effects of gefitinib to VEGF expression were observed in exon 19 deletion stable lung cancer cells (exon 19 deletion vs. wild-type EGFR, P=0.0005). The results of the present study may provide an insight into the association of mutant EGFR and VEGF expression in lung cancer, and may assist with further development of targeted therapy for NSCLC in the future.

Keywords: erpidermal growth factor receptor; lung cancer; mutation; vascular endothelial growth factor.