Glucocorticoid and cAMP induction mechanisms are differentially affected by the p85gag-mos oncoprotein.
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.
Hamilton
B J
BJ
Department of Biological Sciences, University of Pittsburgh, PA 15260.
DeFranco
D
D
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D019256:Cadmium Chloride; D002460:Cell Line; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D015683:Gene Products, gag; D008668:Metallothionein / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D012191:Retroviridae Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013696:Temperature; D013873:Thionucleotides / Q000494:pharmacology*
D015683:Gene Products, gag; D012333:RNA, Messenger; D012191:Retroviridae Proteins; D013873:Thionucleotides; D002104:Cadmium; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D003907:Dexamethasone; D008668:Metallothionein; D000242:Cyclic AMP; D019256:Cadmium Chloride