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Positive autoregulation of ras genes expression in fibroblasts
Author(s) -
Quincoces Ana F.,
Polanco Isidoro,
Thomson Timothy,
León Javier
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01229-5
Subject(s) - autoregulation , microbiology and biotechnology , gene , chemistry , biology , biochemistry , endocrinology , blood pressure
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.