Induction of epidermal growth factor receptor expression and mitogenesis by alcohol in human colon...

Epidemiologic studies suggest that alcohol may be an inducing factor in human colon tumorigenesis. As colon cells are frequently under autocrine control by growth factors, involvement of the EGFR pathway in alcohol-related colon tumor progression was investigated in the human colon adenocarcinoma-derived cell line Caco-2 which shows EGFR distribution mainly in basolateral cell membranes. EGF treatment results in almost complete downregulation of the basolateral receptor. Low concentrations of ethanol (0.22 mM, 0.1%) however, lead to significantly increased EGFR mRNA and protein expression and a raised mitotic rate mainly in basolaterally treated cells. Alcohol-induced overexpression of EGFR is paralleled by increased cyclin D1 expression. This suggests a possible mechanism for low blood levels of alcohol to stimulate in vivo proliferation of colonocytes by elevating transcription of a growth factor receptor as well as by modifying expression of a cell cycle regulator.