Carcinogenesis, Teratogenesis & Mutagenesis ›› 2009, Vol. 21 ›› Issue (1): 30-035.doi: 10.3969/j.issn.1004-616x.2009.01.008

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Leptin Activates ERK1/2 Signaling Pathway and Induces Lung Cancer Cell Proliferation

ZHANG Yan-bei,HUA Tian-feng,HE Feng-lian,FANG Ming,HU Bi-dan, XU Ke, LIU Rong-yu   

  1. Department of Geriatric Pulmonology, The First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui,China
  • Received:2008-08-27 Revised:2008-11-06 Online:2009-01-30 Published:2009-01-30

Abstract: BACKGROUND AND AIM: This study was to evaluate leptin and OB-Rb expression in human lung cancer and adjacent normal lung tissuee,and xplore the role of extracellular singnal-regulated kinase 1/2(ERK1/2) in leptin-induced lung cancer A549 cell proliferation . MATERIALS AND METHODS: Immunohistochemical staining was used to evaluate the protein expression of leptin and OB-Rb in tumor tissues and samples of corresponding adjacent lung tissue,the expression of OB-Rb in A549 cells was evaluated by fluoroimmunoassay and reverse transcription polymerase chain reaction(RT-PCR). The action of leptin on A549 was examined by MTT assay to determine cell proliferation,and activation of extracellular singnal-regulated kinase 1/2(ERK1/2) was assessed by Western blot. RESULTS: The positive protein expression of leptin and OB-Rb were detected in a significantly greater proportion of lung cancer(83.37% and 66.7%,respectively)than adjacent normal lung tissue(33.3% and 29.2%,respectively),P<0.01. Fluoroimmunoassay and RT-PCR showed the presence of OB-Rb in A549 cells. Leptin could stimulate the proliferation of A549 cells,and this effect was maximal at 100 ng/ml after 24-hour treatment. Blocking ERK1/2 phosphorylation by PD98059 significantly reduced the proliferation of A549 cells stimulated by leptin. CONCLUSION: Enhanced expression of leptin and OB-Rb in lung cancer and leptin could promote the proliferation of A549 cells by activating ERK1/2 signaling pathway suggested that continued activation of ERK1/2 pathways by leptin might promote lung cancer growth and development.

Key words: lung cancer, leptin, receptor, ERK1/2, A549, proliferation