Heterozygous mice for the transforming growth factor-beta type II receptor gene have increased susceptibility to hepatocellular carcinogenesis
| Autor: | Y H, Im, H T, Kim, I Y, Kim, V M, Factor, K B, Hahm, M, Anzano, J J, Jang, K, Flanders, D C, Haines, S S, Thorgeirsson, A, Sizeland, S J, Kim |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Heterozygote Gene Dosage Receptor Transforming Growth Factor-beta Type II Protein Serine-Threonine Kinases Genes cdc Mice Inbred C57BL Transforming Growth Factor beta1 Mice Cell Transformation Neoplastic Liver Neoplasms Experimental Liver Pregnancy Transforming Growth Factor beta Phenobarbital Carcinogens Animals Diethylnitrosamine Female Genetic Predisposition to Disease RNA Messenger Receptors Transforming Growth Factor beta |
| Zdroj: | Cancer research. 61(18) |
| ISSN: | 0008-5472 |
| Popis: | The transforming growth factor-beta (TGF-beta) receptor complex and its downstream signaling intermediates constitute a tumor suppressor pathway. In many cancers, expression of TGF-beta type II receptor (TbetaR-II) is markedly decreased. In the present study, we show that the hepatocytes isolated from 15-day-old, but not 9-month-old, mice heterozygous for the deletion of the TbetaR-II gene are slightly less sensitive to the growth-inhibitory effect of TGF-beta when compared with wild-type littermates of same age. In addition, the proliferation index of hepatocytes as indicated by bromodeoxyuridine incorporation is mildly increased in the heterozygous mice. These subtle changes in cellular phenotype did not result in either gross or microscopic abnormality of the liver. The treatment of these mice with the chemical carcinogen, diethylnitrosamine, results in a significantly enhanced tumorigenesis in the liver when compared with the wild-type littermates. Our results demonstrate the gene-dosage effect of TbetaR-II and indicate that the reduced expression of TbetaR-II in mice increases susceptibility to tumorigenesis in the liver. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|