| First Author | Cheung AF | Year | 2010 |
| Journal | Oncogene | Volume | 29 |
| Issue | 12 | Pages | 1857-64 |
| PubMed ID | 20010873 | Mgi Jnum | J:160399 |
| Mgi Id | MGI:4454383 | Doi | 10.1038/onc.2009.457 |
| Citation | Cheung AF, et al. (2010) Complete deletion of Apc results in severe polyposis in mice. Oncogene 29(12):1857-64 |
| abstractText | The adenomatous polyposis coli (APC) gene product is mutated in the vast majority of human colorectal cancers. APC negatively regulates the WNT pathway by aiding in the degradation of beta-catenin, which is the transcription factor activated downstream of WNT signaling. APC mutations result in beta-catenin stabilization and constitutive WNT pathway activation, leading to aberrant cellular proliferation. APC mutations associated with colorectal cancer commonly fall in a region of the gene termed the mutation cluster region and result in expression of an N-terminal fragment of the APC protein. Biochemical and molecular studies have revealed localization of APC/Apc to different sub-cellular compartments and various proteins outside of the WNT pathway that associate with truncated APC/Apc. These observations and genotype-phenotype correlations have led to the suggestion that truncated APC bears neomorphic and/or dominant-negative function that support tumor development. To analyze this possibility, we have generated a novel allele of Apc in the mouse that yields complete loss of Apc protein. Our studies reveal that whole-gene deletion of Apc results in more rapid tumor development than the APC multiple intestinal neoplasia (Apc(Min)) truncation. Furthermore, we found that adenomas bearing truncated Apc had increased beta-catenin activity when compared with tumors lacking Apc protein, which could lead to context-dependent inhibition of tumorigenesis. |
