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 Printable version |
Recent progress on the role of APC protein in the origin of colorectal cancer |
Bulletin du Cancer. Volume 84, Number 11, 1053-60, Novembre 1997, Synthèses
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 Résumé
Article gratuit
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Author(s) : Charlyne Bonneton, Lionel Larue, Jean-Paul Thierry |
Summary : The adenomatous polyposis coli (APC) gene has been found to be mutated during the development of sporadic colorectal cancers as well as in familial adenomatous polyposis (FAP). These conditions result from initially somatic and germ line mutations respectively. In both cases, the expressed protein is truncated at its carboxyterminal region. Investigations into the role of wild-type APC have led to a better understanding of the importance of mutations in the genesis and progression of adenomas. APC was shown to regulate cell growth and cell death, to bind -catenin, and to colocalize with microtubules. APC truncation was therefore hypothesized to alter cell multiplication and cells are no longer able to undergo apoptosis. Owing to its -catenin binding, APC can modify the pool of -catenin which is in part utilized in the assembly of adherens junctions and in nuclear signalling. Truncated APC is unable to regulate this pool thereby altering adhesion and cell signalling. Finally, APC involvement in microtubule-dependent locomotion may explain some changes in cell movement which are observed in adenomas. The establishement of murine mutants and of normal and malignant intestinal cell cultures have allowed to assess biochemical and physiological properties of APC and its putative role in the genesis of colorectal carcinogenesis. Moreover, these experimental models have suggested a variety of possible therapeutic approaches. |
Keywords : adenomatous polyposis coli, APC, FAP, cell division, apoptosis, -catenin, micro-tubules, colon carcinoma. |
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