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Alteration of ß-Catenin Expression in Colonic Epithelial Cells of Familial Adenomatous Polyposis Patients¹

Pathology Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104 [M. I., A. O., S. A., S. H.], Japan, and First Department of Surgery, Oita Medical University, 1-1, Hasama-machi, Oita 879-55 [M. I., S. K.], Japan

It has been found that ß-catenin, a key regulator of the cadherin-mediated cell adhesion system, forms complexes with adenomatous polyposis coli (APC) tumor suppressor protein, and ß-catenin expression levels are affected by exogenously induced APC protein. The effects of intrinsic APC protein alteration on ß-catenin expression levels and its subcellular localization were examined in colonic epithelia of eight patients with familial adenomatous polyposis. In all eight patients, ß-catenin was immunostained at the membranes of the cell-to-cell borders in normal epithelial cells, whereas the nuclei and cytoplasms stained intensely in addition to the membranes in both adenoma and cancer cells. ß-Catenin expression levels in tumor tissues were over three times higher than those in corresponding normal mucosae of all of the three patients, whose resected specimens were available for quantitative immunoblot analysis. In these three patients, mutant truncated APC proteins were detected and shown to have lost the central region, including a known ß-catenin binding domain. ß-Catenin was not coimmunoprecipitated with these mutant APC proteins in tumor tissues but was able to be coprecipitated with glutathione S-transferase-fused APC protein containing a ß-catenin binding domain. These results suggest that the absence of wild-type APC protein affects the subcellular localization and expression levels of ß-catenin in human tissues.

¹ This work was supported in part by a Grant-in-Aid for the 2nd Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health and Welfare of Japan. M.I. is an awardee of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research.

² To whom requests for reprints should be addressed. Phone: 81-3-3542-2511 (Ext. 4201) Fax: 81-3-3248-2737.

Received 11/ 6/95. Accepted 2/27/96.

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