Open AccessGlucocorticoid and cAMP induction mechanisms are differentially affected by the p85gag-mos oncoprotein.
Author(s) -
Byron B. Hamilton,
Donald B. DeFranco
Publication year - 1989
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.86.2.597
Subject(s) - signal transduction , biology , glucocorticoid , gene expression , microbiology and biotechnology , oncogene , cell culture , neoplastic transformation , cell cycle , gene , biochemistry , endocrinology , carcinogenesis , genetics
The inability to perceive and coordinate both internal and external signals that function to regulate cellular growth and proliferation is a hallmark of oncogenic transformation. To examine the effects of the v-mos oncogene on distinct signal transduction pathways, the 6m2 cell line was used, in which expression of the p85gag-mos oncogene, and consequently transformation, are temperature sensitive. Through the analysis of endogenous metallothionein 1 (Mt-1) gene expression in 6m2 cells, p85gag-mos effects on glucocorticoid, cAMP, and heavy-metal induction were examined. While heavy-metal induction of Mt-1 mRNA was found to be unaffected by p85gag-mos, differential effects were exerted upon glucocorticoid and cAMP induction of Mt-1. Glucocorticoid induction of Mt-1 mRNA in p85gag-mos-transformed 6m2 cells was initiated normally but not maintained to the same extent as in nontransformed 6m2 cells. In contrast, cAMP did not induce Mt-1 mRNA in p85gag-mos-transformed 6m2 cells, although a significant induction was noted in nontransformed 6m2 cells. Thus, an oncoprotein interferes with different steps in each particular signal transduction pathway, ultimately causing abnormalities of inducible gene expression.