論文 - 詳細
| RRC ID | 4870 |
|---|---|
| 著者 | Yoshimi K, Tanaka T, Takizawa A, Kato M, Hirabayashi M, Mashimo T, Serikawa T, Kuramoto T. |
| タイトル | Enhanced colitis-associated colon carcinogenesis in a novel Apc mutant rat. |
| ジャーナル | Cancer Sci |
| Abstract |
To establish an efficient rat model for colitis-associated colorectal cancer, azoxymethane and dextran sodium sulfate (AOM/DSS)-induced colon carcinogenesis was applied to a novel adenomatous polyposis coli (Apc) mutant, the Kyoto Apc Delta (KAD) rat. The KAD rat was derived from ethylnitrosourea mutagenesis and harbors a nonsense mutation in the Apc gene (S2523X). The truncated APC of the KAD rat was deduced to lack part of the basic domain, an EB1-binding domain, and a PDZ domain, but retained an intact beta-catenin binding region. KAD rats, homozygous for the Apc mutation on a genetic background of the F344 rat, showed no spontaneous tumors in the gastrointestinal tract. At 5 weeks of age, male KAD rats were given a single subcutaneous administration of AOM (20 mg/kg, bodyweight). One week later, they were given DSS (2% in drinking water) for 1 week. At week 15, the incidence and multiplicity of colon tumors developed in the KAD rat were remarkably severe compared with those in the F344 rat: 100 versus 50% in incidence and 10.7 +/- 3.5 versus 0.8 +/- 1.0 in multiplicity. KAD tumors were dominantly distributed in the rectum and distal colon, resembling human colorectal cancer. Accumulation of beta-catenin protein and frequent beta-catenin mutations were prominent features of KAD colon tumors. To our knowledge, AOM/DSS-induced colon carcinogenesis using the KAD rat is the most efficient to induce colon tumors in the rat, and therefore would be available as an excellent model for human colitis-associated CRC. |
| 巻・号 | 100(11) |
| ページ | 2022-7 |
| 公開日 | 2009-11-1 |
| DOI | 10.1111/j.1349-7006.2009.01287.x |
| PII | CAS1287 |
| PMID | 19694754 |
| MeSH | Animals Codon, Nonsense* Colitis / complications* Colonic Neoplasms / etiology* Colonic Neoplasms / pathology Ethylnitrosourea Female Genes, APC* Male Proto-Oncogene Proteins p21(ras) / genetics Rats Rats, Inbred F344 beta Catenin / genetics |
| IF | 4.966 |
| 引用数 | 28 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ラット | F344-Apcm1Kyo(strainID=714) |