VARIATIONS IN THE EXPRESSION OF THE ADENOMATOUS POLYPOSIS-COLI (APC) TUMOR-SUPPRESSOR GENE IN HUMAN CANCER CELL-LINES OF DIFFERENT TISSUE ORIGIN

The adenomatous polyposis coli (APC) tumor suppressor gene APC is muta ted in familial adenomatous polyposis and in most sporadic colorectal tumors. Through its interaction with beta-catenin the APC protein may play a role in a signal transduction pathway regulating cell prolifera tion. Despite the fact that APC is ubiquitously expressed, mutations l eading to truncated proteins are restricted to rumors of the digestive system. To determine further alterations not resulting in protein tru ncation, but possibly influencing the signaling, we compared the relat ive expression level of the APC protein and transcripts in 24 human co lorectal cancer cell lines and in additional 17 lines of noncolorectal tissue origins, which have not previously been studied. By Western an alysis, the highest levels of full-length APC protein were found in a subset of neuroblastoma and retinoblastoma cell lines. In contrast, in five noncolorectal lines it was not detectable. Truncated APC was exc lusively found in 18 of the 24 colorectal cancer cell lines, but was n ever detected in any cell line derived from other tissues. In most col orectal cancer cell lines the protein level of full-length or mutated APC was reduced. By the more sensitive immunoprecipitation analysis, w eak expression of full-length APC could be shown even in those noncolo rectal cancer cell lines where it was not detectable by Western blotti ng. In addition, APC transcript expression was found in all cell lines , the level in colorectal cancer cell lines being reduced.