Overexpression of transforming growth factor-alpha causes liver enlargement and increased hepatocyte proliferation in transgenic mice.

摘要: Transforming growth factor-alpha (TGF-alpha) expression is associated with hepatocyte DNA replication both in vivo and culture. Our previous work using TGF-alpha transgenic mice showed that constitutive overexpression of this factor the liver causes hepatic tumors 75 to 80% animals at 12 15 months age. To understand cellular events by which leads abnormal growth, we examined proliferative activity young old ploidy normal, dysplastic, neoplastic livers these animals. At 4 weeks age, had higher weights weight/body weight ratios than non-transgenic same age activity, measured 3H-thymidine incorporation after 3- 7-day infusion, proliferating cell nuclear antigen staining, mitotic index determination, was 2 3 times controls. In proliferation declined but decrease much more pronounced control animals, so 8 10 Surprisingly, however, similar ratios. Labeling studies done 3-month-old revealed turnover faster suggesting a homeostatic compensatory mechanism involving death tended restore normal older mice. Ploidy analyses proportion diploid tetraploid hepatocytes hepatocellular developed 13 contained fraction present adjacent tissue or dysplastic livers. The results demonstrate increased enlargement delay establishment polyploidy. These findings as well response partial hepatectomy show initially caused regulated compensated part turnover. may become some expressing hepatocytes.(ABSTRACT TRUNCATED AT 400 WORDS)