Truncated APC is required for cell proliferation and DNA replication.
The tumour suppressor APC is truncated in most colon cancers, which leads to the stabilization of beta-catenin and to the constitutive activation of Wnt signalling. However, it is not clear why colon cancer cells retain the truncated APC fragment. Here, we show that a decrease of APC levels achieved by RNA interference impairs cell proliferation and DNA replication, not only in 293 cells that express a wild-type protein, but also in SW480 colon cancer cells that express exclusively a truncated APC fragment. This correlates with a reduction of the levels of cyclin A, cyclin A-dependent kinase activity, p27(kip1) and the catalytic subunit of DNA polymerase delta. Thus, our data suggest that colon cancer cells retain a truncated APC fragment because it is essential for cell proliferation.
Schneikert
Jean
J
Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, Erlangen, Germany.
Behrens
Jürgen
J
D002453:Cell Cycle; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004258:DNA Polymerase III / Q000378:metabolism; D004261:DNA Replication; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D019925:Cyclin A; D051153:Wnt Proteins; D051176:beta Catenin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011494:Protein Kinases; C102333:histone H1 kinase; D004258:DNA Polymerase III