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Down-Regulation of Carcinoembryonic Antigen Family Member 2 Expression Is an Early Event in Colorectal Tumorigenesis^1,2,

Institute of Immunobiology, University of Freiburg, Stefan-Meier-Strasse 8, D-79104 Freiburg, Germany [J. T., M. S., M. D., C. A., W. Z.], and INSERM U.55, IFR CHU St. Antoine, Hôpital St. Antoine, 75571 Paris, Cedex 12, France [E. C., C. G.]

Carcinoembryonic antigen gene family member 2 (CGM2), a member of the carcinoembryonic antigen (CEA) family, is expressed in normal colon and rectum but is down-regulated in colorectal adenocarcinomas. In situ hybridization studies demonstrate that CGM2 expression is limited to epithelial cells in the upper third of the crypts. Two other CEA family members, biliary glycoprotein (BGP) and nonspecific cross-reacting antigen (NCA), are similarly expressed, whereas CEA transcripts were found down to the base of the crypts but were less predominant in the upper region. Only low CGM2 and BGP mRNA levels were seen in colorectal tumors. CEA mRNA was expressed at an equivalent level in normal epithelia and in tumor cells, whereas NCA transcript levels were up-regulated in tumor cells. Monoclonal antibodies that recognize the CGM2 protein reveal its presence on the apical membranes of epithelial cells in the upper third of the crypts but its absence from colorectal tumors, which do express the CEA and NCA-50/90 proteins. The newly cloned CGM2 3'-untranslated region was used to probe RNAs from adenomas, colorectal tumors at different stages of progression, and liver metastases of colorectal adenocarcinomas. This showed that CGM2 is already down-regulated in adenomas when compared to normal mucosae. The CGM2 expression pattern along with its sequence homology to BGP suggests a similar tumor suppressor function for CGM2.

¹ This work was supported by the Dr. Mildred Scheel Stiftung für Krebsforschung foundation.

² GenBank accession number of the submitted sequence is X98311.

³ To whom requests for reprints should be addressed.

Received 11/12/96. Accepted 3/ 1/97.

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