Mucin 1 (MUC1) signalling contributes to increase the resistance to cell death in human bronchial epithelial cells exposed to nickel acetate

Publication Type:
Journal Article
BioMetals, 2014, 27 (6), pp. 1149 - 1158
Issue Date:
Full metadata record
Files in This Item:
Filename Description Size
10.1007%2Fs10534-014-9776-x.pdfPublished Version806.92 kB
Adobe PDF
© Springer Science+Business Media 2014. We have previously reported that nickel acetate (Ni2+), a well-known human carcinogenic agents, differentially affected apoptosis in two different airway epithelial cell lines derived from the human respiratory tract (A549 and Beas-2B, respectively), suggesting a potential involvement of epidermal growth factor receptor (EGFR)/Neu receptors in mediating this effect. Since ErbBs are closely associated to Mucin 1 (MUC1), a glycoprotein component of airway mucus that is overexpressed in lung tumors, we have investigated the role of this signaling system in the survival response of airway epithelial cells against Ni2+-induced cell death. We found that A549 cells exposed to Ni2+ do not show any significant increase of MUC1 levels. Conversely, Beas-2B cells exposed to equivalent concentrations of Ni2+ showed increased expression of MUC1 levels and this correlated with increased phosphorylation of both EGFR and of the extracellular-regulated kinase 1/2 (ERK1/2) and increase resistance to apoptosis, as indicated by cell viability assessments and DNA damage. Interestingly, suppression of MUC1 by small interfering RNA inhibited the EGFR activation in Beas-2B cells, leading to a significant decrease of survival and enhancement of DNA fragmentation and cleaved Caspase-3 expression. These results strongly suggest a role for MUC1 in Ni2+-induced neoplastic transformation, which likely involves the activation of the EGFR-mediated cell survival pathway, highlighting new avenues in the molecular approach to lung cancer prevention.
Please use this identifier to cite or link to this item: