Differential methylation of the c-H-ras gene in normal mouse cells and during skin tumour progression.
AUTOR(ES)
Ramsden, M
RESUMO
We have previously shown that the mouse c-H-ras gene acquires transforming activity in chemically induced skin tumours. We have now investigated the pattern of DNA methylation at HpaII and XhoI sites around the c-H-ras locus in various tissues and stages of epidermal tumour progression. The results of this study suggest a correlation between the methylation state of the c-H-ras gene and its susceptibility to oncogenic conversion by a point-mutation. The locus is substantially undermethylated in normal epidermis in comparison with NIH/3T3 fibroblasts. Intermediate levels of methylation were observed in the other tissues investigated. The undermethylation at HpaII sites in epidermal DNA persists through the morphologically distinct phases of hyperplasia, benign papilloma and malignant carcinoma. Methylation at a specific XhoI site close to the c-H-ras gene is significantly reduced with respect to normal epidermis in some, but not all epidermal tumours. The methylation state of the c-H-ras locus in specific tumours is stably maintained following transfection of these DNAs into NIH/3T3 cells and selection of transformed foci. Demethylation of the locus is not essential in vitro for the transforming activity of DNA from epidermal tumours. The significance of changes in the methylation pattern of the c-H-ras gene in different tissues and during tumour progression is discussed.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=554366Documentos Relacionados
- Relating aromatic hydrocarbon-induced DNA adducts and c-H-ras mutations in mouse skin papillomas: the role of apurinic sites.
- Mitogenic effects of the proto-oncogene and oncogene forms of c-H-ras DNA in human diploid fibroblasts.
- Isolation of recessive (mediator-) revertants from NIH 3T3 cells transformed with a c-H-ras oncogene.
- A splicing enhancer in the 3'-terminal c-H-ras exon influences mRNA abundance and transforming activity.
- Roles of hnRNP A1, SR Proteins, and p68 Helicase in c-H-ras Alternative Splicing Regulation