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Heterozygous mice for the transforming growth factor-beta type II receptor gene have increased susceptibility to hepatocellular carcinogenesis.
- Source :
-
Cancer research [Cancer Res] 2001 Sep 15; Vol. 61 (18), pp. 6665-8. - Publication Year :
- 2001
-
Abstract
- 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.
- Subjects :
- Animals
Carcinogens
Diethylnitrosamine
Female
Gene Dosage
Genes, cdc physiology
Genetic Predisposition to Disease
Heterozygote
Liver drug effects
Liver metabolism
Liver physiology
Liver Neoplasms, Experimental chemically induced
Liver Neoplasms, Experimental metabolism
Male
Mice
Mice, Inbred C57BL
Phenobarbital pharmacology
Pregnancy
Protein Serine-Threonine Kinases
RNA, Messenger biosynthesis
RNA, Messenger genetics
Receptor, Transforming Growth Factor-beta Type II
Receptors, Transforming Growth Factor beta biosynthesis
Transforming Growth Factor beta biosynthesis
Transforming Growth Factor beta genetics
Transforming Growth Factor beta1
Cell Transformation, Neoplastic genetics
Liver Neoplasms, Experimental genetics
Receptors, Transforming Growth Factor beta genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 61
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 11559531