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Cellular Ras partly mediates gap junction closure by the polyoma virus middle tumor antigen
H L Brownell1, J F Whitfield, L Raptis
1Department of Microbiology, Queen's University, Kingston, Ontario, Canada.
Abstract:
Endogenous, cellular Ras proteins (c-Ras) mediate the transforming action of the polyoma virus middle Tumor antigen (mT), which is accompanied by elimination of gap junctional, intercellular communication (GJIC). In this report we show that reducing the c-Ras content of murine C3H10T1/2 fibroblasts (10T1/2) through the expression of an anti-sense ras gene, increased GJIC by 60-80% mT totally eliminated GJIC in normal 10T1/2 cells but it reduced GJIC no more than 50% in the c-Ras deficient lines. These results indicate that endogenous c-Ras is at least partly responsible for the mT-induced gap junction closure.
Insights
Cellular Ras proteins (c-Ras) are key to polyoma virus middle Tumor antigen (mT) transforming action. Reducing c-Ras levels significantly increased gap junctional intercellular communication (GJIC), suggesting c-Ras partially causes mT-induced gap junction closure.
Area of Science:
- Cellular biology
- Virology
- Molecular oncology
Background:
- Endogenous cellular Ras proteins (c-Ras) are crucial mediators of viral transformation.
- Polyoma virus middle Tumor antigen (mT) is known to induce cellular transformation and disrupt intercellular communication.
- Gap junctional intercellular communication (GJIC) is essential for coordinating cellular functions and is often impaired in cancer cells.
Purpose of the Study:
- To investigate the role of endogenous c-Ras in mediating the effects of polyoma virus mT on GJIC.
- To determine if reducing c-Ras levels can restore or enhance GJIC in the presence of mT.
Main Methods:
- Utilized murine C3H10T1/2 fibroblasts (10T1/2) engineered to express an anti-sense ras gene to reduce endogenous c-Ras levels.
- Quantified GJIC in both normal and c-Ras deficient 10T1/2 cells treated with polyoma virus mT.
- Compared the extent of GJIC inhibition by mT in cells with normal versus reduced c-Ras content.
Main Results:
- Expression of an anti-sense ras gene led to a 60-80% increase in GJIC in 10T1/2 fibroblasts.
- Polyoma virus mT completely eliminated GJIC in normal 10T1/2 cells.
- In c-Ras deficient 10T1/2 cells, mT reduced GJIC by no more than 50%.
Conclusions:
- Endogenous c-Ras plays a significant role in the mT-induced closure of gap junctions.
- Reducing c-Ras levels can partially rescue GJIC from the inhibitory effects of polyoma virus mT.
- These findings highlight a molecular link between c-Ras, viral transformation, and intercellular communication disruption.