Other
11 Authors
- Ito Y,
- Strasser A,
- Ito K,
- Chi XZ,
- Bouillet P,
- Bae SC,
- Ida H,
- Wee HJ,
- Fukamachi H,
- Yano T,
- Inoue K
| First Author | Yano T | Year | 2006 |
| Journal | Mol Cell Biol | Volume | 26 |
| Issue | 12 | Pages | 4474-88 |
| PubMed ID | 16738314 | Mgi Jnum | J:109611 |
| Mgi Id | MGI:3629361 | Doi | 10.1128/MCB.01926-05 |
| Citation | Yano T, et al. (2006) The RUNX3 tumor suppressor upregulates Bim in gastric epithelial cells undergoing transforming growth factor beta-induced apoptosis. Mol Cell Biol 26(12):4474-88 |
| abstractText | Genes involved in the transforming growth factor beta (TGF-beta) signaling pathway are frequently altered in several types of cancers, and a gastric tumor suppressor RUNX3 appears to be an integral component of this pathway. We reported previously that apoptosis is notably reduced in Runx3-/- gastric epithelial cells. In the present study, we show that a proapoptotic gene Bim was transcriptionally activated by RUNX3 in the gastric cancer cell lines SNU16 and SNU719 treated with TGF-beta. The human Bim promoter contains RUNX sites, which are required for its activation. Furthermore, a dominant negative form of RUNX3 comprised of amino acids 1 to 187 increased tumorigenicity of SNU16 by inhibiting Bim expression. In Runx3-/- mouse gastric epithelium, Bim was down-regulated, and apoptosis was reduced to the same extent as that in Bim-/- gastric epithelium. We confirmed comparable expression of TGF-beta1 and TGF-beta receptors between wild-type and Runx3-/- gastric epithelia and reduction of Bim in TGF-beta1-/- stomach. These results demonstrate that RUNX3 is responsible for transcriptional up-regulation of Bim in TGF-beta-induced apoptosis. |
