H-ras activation in benign and self-regressing skin tumors (keratoacanthomas) in both humans and an animal model system
| Autor: | Angel Pellicer, Hideko Kamino, Javier León, J J Steinberg |
|---|---|
| Rok vydání: | 1988 |
| Předmět: |
Male
9 10-Dimethyl-1 2-benzanthracene Biology medicine.disease_cause Skin Diseases Gene product Nude mouse medicine Animals Humans Molecular Biology Gene Regulation of gene expression Mutation Point mutation Cell Biology Transfection Middle Aged biology.organism_classification Disease Models Animal Keratoacanthoma Cell Transformation Neoplastic Genes ras Gene Expression Regulation Immunology Cancer research Rabbits Carcinogenesis Research Article |
| Zdroj: | Molecular and Cellular Biology. 8:786-793 |
| ISSN: | 1098-5549 0270-7306 |
| DOI: | 10.1128/mcb.8.2.786 |
| Popis: | The involvement of the ras oncogenes in tumorigenesis was investigated in keratoacanthomas, which are benign and self-regressing skin tumors, both in humans and in a corresponding animal model system. Keratoacanthomas were induced on rabbit ears by repeated applications of 7,12-dimethylbenz(a)anthracene. About 60% of the tumor DNAs produced transformed foci after transfection into NIH 3T3 cells, and in all of them the transforming gene was identified as H-ras by Southern and Northern (RNA) hybridization. Immunoprecipitation experiments suggested that the transforming rabbit H-ras protein carried a mutation in codon 61. In addition, an activated H-ras gene was detected in a human keratoacanthoma by using a nude mouse tumorigenesis assay after transfection of tumor DNA into NIH 3T3 cells. This is the first report of ras activation in a benign human tumor. The transforming human H-ras gene showed a point mutation in codon 61 that would result in leucine instead of the glutamine present in the normal gene product. The finding of ras activation in tumors that are not only benign but also self-regressing indicates that activated ras genes are not sufficient to maintain a neoplastic phenotype, although they likely play a role in early stages of tumorigenesis. |
| Databáze: | OpenAIRE |
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