Positive autoregulation of ras genes expression in fibroblasts

FEBS Letters

León, Javier¹  Quincoces, Ana F.¹  Thomson, Timothy²  Polanco, Isidoro¹ 

[1] Departamento de Biologı́a Molecular, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain;Instituto de Biologı́a del Cáncer, UBCM-IMIM, Doctor Aiguader 80, 08003 Barcelona, Spain

关键词: ras gene;    Dexamethasone;    Autoregulation;    Gene expression;    Fibroblast;   

DOI  :  10.1016/S0014-5793(97)01229-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown