Although it is well known that
epidermal growth factor receptor (EGFR) is involved in
lung cancer progression, whether EGFR contributes to lung epithelial cell transformation is less clear.
Mucin 1 (MUC1 in human and Muc1 in animals), a
glycoprotein component of airway mucus, is overexpressed in lung
tumors; however, its role and underlying mechanisms in early stage lung
carcinogenesis is still elusive. This study provides strong evidence demonstrating that EGFR and MUC1 are involved in bronchial epithelial cell transformation. Knockdown of MUC1 expression significantly reduced transformation of immortalized human bronchial epithelial cells induced by
benzo[a]pyrene diol
epoxide (
BPDE), the active form of the cigarette
smoke (CS)
carcinogen benzo(a)pyrene (BaP)s.
BPDE exposure robustly activated a pathway consisting of EGFR, Akt and ERK, and blocking this pathway significantly increased
BPDE-induced cell death and inhibited cell transformation. Suppression of MUC1 expression resulted in EGFR destabilization and inhibition of the
BPDE-induced activation of Akt and ERK and increase of cytotoxicity. These results strongly suggest an important role for EGFR in
BPDE-induced transformation, and substantiate that MUC1 is involved in
lung cancer development, at least partly through mediating
carcinogen-induced activation of the EGFR-mediated cell survival pathway that facilitates cell transformation.