THE EXPRESSION OF MOUSE BILIARY GLYCOPROTEIN, A CARCINOEMBRYONIC ANTIGEN-RELATED GENE, IS DOWN-REGULATED IN MALIGNANT MOUSE-TISSUES

Mouse biliary glycoprotein (Bgp) is a member of the carcinoembryonic a ntigen gene family and is highly expressed in the epithelial cells of normal hepatic biliary ducts and intestine. Nine mouse Bgp isoforms ha ve been identified through molecular cloning and shown to be splice an d allelic variants of one Bgp gene. These glycoproteins function in vi tro as intercellular adhesion molecules and serve as the mouse hepatit is virus receptors. Since human carcinoembryonic antigen is overexpres sed in gastrointestinal tumors, we have investigated the expression of mouse Bgp in primary tumors and carcinoma cell lines. Our results dem onstrate that the expression of the major mouse Bgp isoforms is down-r egulated in tumors at the transcriptional and the posttranscriptional levels. This decrease in expression is corroborated by immunostaining of primary colonic tumors with anti-mouse Bgp antibodies. In addition, Bgp expression is influenced by transcriptional control mechanisms in volving DNA methylation of the Bgp gene upstream regulatory region. Ou r results demonstrate that mouse Bgp protein expression is decreased u pon malignant transformation and further suggest that Bgp proteins may be involved in the maintenance of the differentiated cellular phenoty pe.