Epidermal growth factor receptor (EGFR) and neuregulin (Neu) activation in human airway epithelial cells exposed to nickel acetate.
Nickel compounds are potential carcinogenic agents that produce a range of biological effects, including inhibition of cell death. Because suppression of apoptosis is thought to contribute to the initiation of carcinogenesis, we investigated the effects of nickel acetate (Ni(2+)) treatment on apoptosis in two different airway epithelial cell lines (A549 and Beas-2B, respectively). Furthermore, since both the epidermal growth factor receptor (EGFR) and neuregulin (Neu) are involved in neoplastic development, mRNAs and expression levels of total and phosphorylated proteins (p-EGFR(Tyr1173) and p-Neu(Tyr1248), respectively) were also measured. We found that exposure of A549 cells to Ni(2+) resulted in significantly reduced cell viability, as well as increased apoptosis and DNA fragmentation at relatively low concentrations (0.1 and 0.5mM) after 24 and 48h. These changes were accompanied by reduced EGFR and Neu mRNAs and proteins, phosphorylated proteins as well as decreased Bcl-2 and increased BAX protein expression. Conversely, Beas-2B cells exposed to equivalent concentrations of Ni(2+) did not show evident signs of apoptosis and DNA damage, hence showing increased expression and phosphorylation of both EGFR and Neu, increased Bcl-2 and reduced BAX expression. Altogether, our finding indicate that Ni(2+) exposure differently affects apoptosis initiation either in non-tumorigenic (Beas-2B) and tumorigenic airway epithelial cells (A549), suggesting a potential involvement of EGFR/Neu receptors.
Department of Bio-Medical Sciences, University of Catania, Catania, Italy.
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Giunta
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Castorina
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Scuderi
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Patti
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D'Agata
D000085:Acetates / Q000633:toxicity*; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020880:Neuregulins / Q000235:genetics / Q000378:metabolism*; D009942:Organometallic Compounds / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000085:Acetates; D000395:Air Pollutants, Occupational; C494826:BAX protein, human; D020880:Neuregulins; D009942:Organometallic Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C119536:nickel acetate; D066246:ErbB Receptors