The adenomatous polyposis coli (APC) tumor suppressor gene APC is mutated 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 proliferation. Despite the fact that APC is ubiquitously expressed, mutations leading to truncated proteins are restricted to tumors of the digestive system. To determine further alterations not resulting in protein truncation, but possibly influencing the signaling, we compared the relative expression level of the APC protein and transcripts in 24 human colorectal cancer cell lines and in additional 17 lines of noncolorectal tissue origins, which have not previously been studied. By Western analysis, 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 exclusively found in 18 of the 24 colorectal cancer cell lines, but was never detected in any cell line derived from other tissues. In most colorectal cancer cell lines the protein level of full-length or mutated APC was reduced. By the more sensitive immunoprecipitation analysis, weak expression of full-length APC could be shown even in those noncolorectal cancer cell lines where it was not detectable by Western blotting. In addition, APC transcript expression was found in all cell lines, the level in colorectal cancer cell lines being reduced.