This study provides strong evidence supporting a cancer-promoting role of MUC1 in CS-induced lung carcinogenesis: MUC1 potentiated transformation of human bronchial cells induced by the tobacco carcinogen BPDE; BPDE markedly activated EGFR and its downstream pathways Akt and ERK, and blocking these pathways significantly increased BPDE-induced cytotoxicity and inhibited cell transformation; Suppression of MUC1 expression destabilized EGFR protein and inhibited BPDE-induced activation of EGFR, Akt and ERK, and subsequently increased BPDE-induced cell death. The gene discussed is EGFR; the disease is cancer.