| First Author | Sanders S | Year | 2000 |
| Journal | Mol Carcinog | Volume | 28 |
| Issue | 3 | Pages | 168-73 |
| PubMed ID | 10942533 | Mgi Jnum | J:64633 |
| Mgi Id | MGI:1889725 | Doi | 10.1002/1098-2744(200007)28:3<168::aid-mc5>3.0.co;2-e |
| Citation | Sanders S, et al. (2000) Promotion of hepatocarcinogenesis by phenobarbital in c-myc/TGF-alpha transgenic mice. Mol Carcinog 28(3):168-73 |
| abstractText | Previous work has shown that phenobarbital (PB) can promote cell survival in double transgenic c-myc/transforming growth factor (TGF)-alpha mice. This was achieved through a suppression of cell death brought about, at least in part, by a general increase in the level of bcl-2 protein and a decrease in TGF-beta1 in treated versus untreated animals. No changes were found in TGF-beta type II receptor or in bcl-X(L) protein levels. In the present work, we followed these animals for up to 31 wk of age (28 wk of treatment), by which time numerous tumors could be observed. A PB-dependent decrease in tumor latency and a significant increase in multiplicity were seen. No statistically significant changes in the phenotype of foci, nodules, or neoplasms were observed after PB administration, and no effect on median tumor size was detected. Levels of the anti-apoptotic protein bcl-2 did not correlate with tumor formation in PB-treated animals. However, in untreated mice, bcl-2 was higher in tumors than in surrounding tissue in all tumors examined. We believe that the PB-dependent modification of tumorigenesis in the livers of c-myc/TGF-alpha mice was predominantly a result of the ability of this drug to block cell death during the early stages of tumor development. The effect of PB was exerted apparently by a pathway similar to, but separate from, that of TGF-alpha. However, these pathways appear to converge downstream, having common effectors in the form of bcl-2 family proteins. Mol. Carcinog. 28:168-173, 2000. Copyright 2000 Wiley-Liss, Inc. |
