title: Mucin 1 (MUC1) signalling contributes to increase the resistance to cell death in human bronchial epithelial cells exposed to nickel acetate.
abstract: We have previously reported that nickel acetate (Ni(2+)), 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 Ni(2+)-induced cell death. We found that A549 cells exposed to Ni(2+) do not show any significant increase of MUC1 levels. Conversely, Beas-2B cells exposed to equivalent concentrations of Ni(2+) 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 Ni(2+)-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.
authors: Department of Bio-Medical Sciences, Section of Anatomy and Histology, University of Catania, Via S.Sofia, 87, 95123, Catania, Italy.
authors: Alessandro
authors: A
authors: Castorina
authors: Salvatore
authors: S
authors: Giunta
mesh_terms: D000085:Acetates / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000166:cytology*; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects*; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D018396:Mucin-1 / Q000235:genetics / Q000502:physiology*; D009707:Nucleosomes / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000085:Acetates; D002273:Carcinogens; C060192:MUC1 protein, human; D018396:Mucin-1; D009707:Nucleosomes; D009942:Organometallic Compounds; D034741:RNA, Small Interfering; C119536:nickel acetate; C512478:EGFR protein, human; D066246:ErbB Receptors