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The Expression of Mouse Biliary Glycoprotein, a Carcinoembryonic Antigen-related Gene, Is Down-Regulated in Malignant Mouse Tissues¹

McGill Cancer Center [M. R., P. N., C. T., N. B.], Departments of Biochemistry [M. R., N. B.], Pathology [S. J.], Surgery [D. F.], Medicine [P. N., N. B.] and Oncology [N. B.], McGill University, Montréal, Québec, Canada

Mouse biliary glycoprotein (Bgp) is a member of the carcinoembryonic antigen gene family and is highly expressed in the epithelial cells of normal hepatic biliary ducts and intestine. Nine mouse Bgp isoforms have been identified through molecular cloning and shown to be splice and allelic variants of one Bgp gene. These glycoproteins function in vitro as intercellular adhesion molecules and serve as the mouse hepatitis virus receptors. Since human carcinoembryonic antigen is overexpressed in gastrointestinal tumors, we have investigated the expression of mouse Bgp in primary tumors and carcinoma cell lines. Our results demonstrate that the expression of the major mouse Bgp isoforms is down-regulated 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 involving DNA methylation of the Bgp gene upstream regulatory region. Our results demonstrate that mouse Bgp protein expression is decreased upon malignant transformation and further suggest that Bgp proteins may be involved in the maintenance of the differentiated cellular phenotype.

¹ Supported by grants from the Medical Research Council of Canada and from the Cancer Research Society, Inc.

² M. R. and P. N. contributed equally to this article and should both be considered as first authors, M. R. is the recipient of a studentship from the Cancer Research Society, Inc., and P. N. is the recipient of a studentship from the Institut Mérieux, Lyon, France.

³ N. B. is a scholar of the Fonds de la Recherche en Santé du Québec.

⁴ To whom requests for reprints should be addressed, at McGill Cancer Center, McGill University, 3655 Drummond Street, Montréal, Québec, H3G 1Y6, Canada.

Received 4/26/93. Accepted 8/11/93.

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