Bisphenol A stimulates human lung cancer cell migration via upregulation of matrix metalloproteinases by GPER/EGFR/ERK1/2 signal pathway |
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| Affiliation: | 1. Division of Occupational and Environmental Health, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China;2. Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong, China;3. Family Medicine Training Centre, Prince of Wales Hospital, Hong Kong, China;4. Department of Surgery, Prince of Wales Hospital, Hong Kong, China;5. Guilin Medical College, Guangxi Province, China;6. Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China;7. Department of Health Science and Recreation, San Jose State University, USA;8. Dalla Lana School of Public Health a Faculty of the University of Toronto, Canada;9. School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai 200032, China;10. SH Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China |
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| Abstract: | Lung cancer is one of the leading causes of cancer deaths worldwide. Recent evidences indicated that bisphenol A (BPA), a wide contaminant with endocrine disrupting activity, could enhance the susceptibility of carcinogenesis. Although there are increasing opportunities for lung cells exposure to BPA via inhalation, there is no study concerning the effects of BPA on the development of lung cancer. The present study revealed that BPA less than 10−4 M had limited effects on the proliferation of lung cancer A549 cells, however, BPA treatment significantly stimulated the in vitro migration and invasion of cells combing with the morphological changes and up regulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. G-protein-coupled estrogen receptor (GPER), while not estrogen receptor α/β (ERα/β), mediated the BPA induced up regulation of MMPs. Further, BPA treatment induced rapid activation of ERK1/2 via GPER/EGFR. GPER/ERFR/ERK1/2 mediated the BPA induced upregulation of MMPs and in vitro migration of lung cancer A549 cells. In summary, our data presented here revealed for the first time that BPA can promote the in vitro migration and invasion of lung cancer cells via upregulation of MMPs and GPER/EGFR/ERK1/2 signals, which mediated these effects. This study suggested that more attention should be paid on the BPA and other possible environmental estrogens induced development of lung cancer. |
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| Keywords: | BPA Lung cancer Migration MMP |
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