[Current data on the role of APC protein in the origin of colorectal cancer].
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 beta-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 beta-catenin binding, APC can modify the pool of beta-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 establishment 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.
Bonneton
C
C
UMR 144 du CNRS et de l'Institut Curie, Compartimentation et dynamique cellulaires, Paris.
Larue
L
L
Thiery
J P
JP
D011125:Adenomatous Polyposis Coli / Q000150:complications / Q000235:genetics*; D000818:Animals; D002468:Cell Physiological Phenomena; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D017491:Genes, APC / Q000235:genetics*; D006801:Humans; D009154:Mutation; D051381:Rats; D012004:Rectal Neoplasms / Q000209:etiology / Q000235:genetics*; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin
Données récentes sur le rôle de la protéine APC dans la genèse du cancer colorectal.