Evidence for the Colonic Origin of Ovarian Cancer Cell Line SW626

Cancer cell lines are an essential tool of cancer research, but their origin can sometimes be difficult to determine with certainty. In addition to contamination with other cell lines during in vitro cultivation, errors can arise during the initial resection from the patient because the organ of origin can sometimes be difficult to determine. This is particularly problematic for ovarian cancer, where a substantial fraction of the cases represent metastases from distant nongenital sites ( 1 ). Once in culture and without detailed patient data, it can be difficult or impossible to trace the origin of a particular cell population. The difficulty arises from the fact that cells tend to lose their tissue-specific markers during tumorigenesis and in vitro establishment. In the course of our study of β-catenin signaling in ovarian cancer, we discovered several ovarian cancer lines that have constitutively elevated β-catenin-mediated transcription (Furlong MT, Morin PJ: unpublished results). Deregulation of this pathway results in inappropriate activation of T-cell factor-responsive genes and, in colon cancer, is due to mutations either in β-catenin or in the tumor suppressor gene adenomatous polyposis coli (APC) ( 2 , 3 ). Our finding of ovarian cell lines with an activated β -catenin/T-cell factor pathway is consistent with a recent report ( 4 ) that β-catenin is mutated in a subset of ovarian cancers. SW626, a well-studied ovarian cancer cell line, showed high levels of β-catenin-mediated transcriptional activation but contained a wild-type β-catenin gene, as assessed by direct sequencing. Surprisingly, however, when a cell lysate of SW626 was probed by immunoblotting with an anti-APC antibody, full-length APC was not detected (Fig. 1, A). Instead, SW626 expressed a truncated product of approximately 110 kd. The APC tumor suppressor gene is mutated in the vast majority of all colon cancers ( 5 ) but has never been found to be altered in ovarian cancer. Indeed, APC was previously analyzed in 40 sporadic ovarian carcinomas, and no mutations were found ( 6 ).