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Glucocorticoid and cAMP induction mechanisms are differentially affected by the p85gag-mos oncoprotein
1Department of Biological Sciences, University of Pittsburgh, PA 15260.
Abstract:
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.
Insights
Oncogenic transformation disrupts cellular growth signals. The v-mos oncogene interferes with specific signal transduction pathways, affecting metallothionein 1 gene expression and leading to abnormal inducible gene expression.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- Oncogenic transformation is characterized by a loss of control over cellular growth and proliferation signals.
- Signal transduction pathways are crucial for regulating cellular responses to internal and external cues.
- The v-mos oncogene is implicated in cellular transformation and aberrant signaling.
Purpose of the Study:
- To investigate the impact of the v-mos oncogene on distinct signal transduction pathways.
- To analyze the effects of p85gag-mos expression on metallothionein 1 (Mt-1) gene induction.
- To understand how oncogene expression alters cellular responses to specific signaling molecules.
Main Methods:
- Utilized the temperature-sensitive 6m2 cell line for controlled expression of the p85gag-mos oncogene.
- Examined endogenous metallothionein 1 (Mt-1) gene expression as a readout for signal transduction pathway activity.
- Assessed the induction of Mt-1 mRNA by glucocorticoid, cAMP, and heavy metals in both transformed and non-transformed cells.
Main Results:
- Heavy-metal induction of Mt-1 mRNA remained unaffected by p85gag-mos expression.
- Glucocorticoid induction of Mt-1 mRNA was initiated but not sustained in p85gag-mos-transformed cells.
- cAMP failed to induce Mt-1 mRNA in p85gag-mos-transformed cells, unlike in non-transformed cells.
Conclusions:
- The p85gag-mos oncoprotein differentially interferes with glucocorticoid and cAMP signal transduction pathways.
- Abnormalities in inducible gene expression are a consequence of oncoprotein-mediated disruption of signaling.
- Oncogenic transformation leads to a breakdown in the coordination of cellular growth regulation signals.