OBJECTIVE: To determine the role of extracellular signal regulated kinase (ERK) signaling pathway in SiO₂ induced epithelial-mesenchymal transition (EMT) in human bronchial epithelial cells (HBEC) in vitro. METHODS: HBEC were treated with SiO₂ (0-300 μg/mL) for 72 h or pretreated with U0126 (0-30 μmol/L) for 1 h and then treated with 200 μg/mL SiO₂ for 72 h. Western blot was used to detect the protein expression of E-cadherin and α-smooth muscle actin (α-SMA). The activity of ERK was examined by mitogen-activated protein kinase (MAPK) activity assay kit in HBEC exposing to SiO₂ (200 μg/mL) for 0-8 h. RESULTS: The expression of E-cadherin decreased gradually in SiO₂ -stimulated HBEC, and the effect was most significant at 300 μg/mL (P<0.01). The expression of α-SMA increased and the effect was most evident at 200 μg/mL (P<0.01). With SiO₂ treatment, the activity of ERK was upregulated significantly. The phosphorylation of ERK increased at 30 min and decreased after 1 h. U0126 significantly inhibited SiO₂ -induced expression changes in E-cadherin and α-SMA. At 30 μmol/L, the effect was most evident(P<0.01). CONCLUSION ERK signaling pathway mediated EMT induced by SiO₂ in HBEC.
Actins ; metabolism ; Bronchi ; cytology ; Cadherins ; metabolism ; Cell Transdifferentiation ; drug effects ; Cells, Cultured ; Epithelial Cells ; cytology ; physiology ; Epithelial-Mesenchymal Transition ; Humans ; MAP Kinase Signaling System ; physiology ; Mitogen-Activated Protein Kinases ; metabolism ; Silicon Dioxide ; pharmacology

OBJECTIVE: To investigate the expression of fibroblast growth factor-2 (FGF-2) and osteopontin (OPN) in non-small cell lung cancer (NSCLC) tissues and analyze the correlation between FGF-2 and OPN. METHODS: Immunohistochemical SP method was used to detect the expression of FGF-2 and OPN in 76 patients with NSCLC and 15 normal lung tissues. The effect of FGF-2 on OPN expression at mRNA and protein level in A549 cell was examined by RT-PCR and Western blot. RESULTS: The positive expression of FGF-2 (65.8%) and OPN (60.5%) in the NSCLC tissues was significantly higher than that in the normal lung tissues (13.3% and 0, respectively ) (P<0.01). The expression of FGF-2 and OPN was closely related to TNM stages and the lymph node metastasis (all Ps<0.01), but not to histological types, sex, and age of NSCLC patients (all Ps>0.05).A positive correlation was found between the expression of FGF-2 and OPN in NSCLC (r=0.552,P<0.01). The expression of OPN protein and mRNA was up-regulated by FGF-2 in A549 cells. CONCLUSION The overexpression of FGF-2 and OPN is related to the metastasis and invasion of NSCLC.FGF-2 may promote the metastasis and invasion of NSCLC depending on the upregulation of OPN expression.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Female ; Fibroblast Growth Factor 2 ; genetics ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Osteopontin ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism