Positive autoregulation of ras genes expression in fibroblasts.
We have studied the effect of ectopic overexpression of a ras gene on the expression of the other two members of the ras gene family. We obtained NIH3T3 cell lines stably transfected with inducible H-ras and N-ras oncogenes. The expression of these genes is driven by a glucocorticoid-responsive promoter and the addition of dexamethasone resulted in a dramatic induction (10-20-fold) of H- or N-ras mRNA, peaking 4 h after hormone addition. The induction of the expression of ras oncogenes resulted in a transformed phenotype. In quiescent NIH3T3 cells transfected with inducible H-ras oncogenes, the induction of H-Ras was followed 12 h later by a 3-fold increase in the mRNA expression of endogenous K-ras and N-ras. Similarly, in NIH3T3 transfected with inducible N-ras oncogene, the induction of N-ras was followed by an increase in the expression of endogenous K- and H-ras genes. Interestingly, the effect was not limited to the mutated N-ras, as a similar result was obtained in cells transfected with N-ras proto-oncogene. The induction of ras genes expression was not linked to cell cycle progression as it was reproduced in cells arrested in S-phase by pretreatment with hydroxyurea. These results suggest the presence of a positive cross-regulation in the expression among the members of the Ras family. This effect could play a role in Ras-mediated carcinogenesis.
Quincoces
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AF
Departamento de Biología Molecular, Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
Polanco
I
I
Thomson
T
T
León
J
J
D016475:3T3 Cells; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras; D006706:Homeostasis; D007700:Kinetics; D051379:Mice; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D012333:RNA, Messenger; D003907:Dexamethasone; D015689:Oncogene Protein p21(ras)