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Published on: October 27, 2020
Involvement of the TGF-beta and mTOR/p70S6Kinase pathways in the transformation process induced by v-ErbA
S Gonin-Giraud1, C Bresson-Mazet, O Gandrillon
1Université de Lyon, Lyon, France. gonin@cgmc.univ-lyon1.fr
Abstract:
v-ErbA is the oncogenic form of TRalpha/c-ErbA which transforms chicken erythrocytic progenitors by blocking differentiation. The oncogenic property of v-ErbA has been correlated with its ability to antagonize ligand-dependent gene activation by TRalpha/c-ErbA and retinoic acid receptors. Nevertheless, its cytoplasmic retention suggests that v-ErbA could interfere with intracellular signaling pathways. We demonstrate that only the transforming form of v-ErbA confers to chicken erythroid progenitors a TGF-beta independency and induces an activation of the mTOR/p70S6K pathway. In these cells, TGF-beta and mTOR/p70S6K pathways regulate the expression of a known target gene of v-ErbA, band3. This is the first demonstration that v-ErbA is able to modulate specifically some signaling pathways leading to changes in the expression level of a gene involved in transformation.
Insights
The oncogenic v-ErbA protein transforms cells by blocking differentiation and activating the mTOR/p70S6K pathway, conferring TGF-beta independency. This study reveals v-ErbA
Area of Science:
- Oncogenic signaling
- Molecular biology
- Cellular transformation
Background:
- v-ErbA, the oncogenic form of TRalpha/c-ErbA, blocks erythroid progenitor differentiation.
- Its oncogenic potential is linked to antagonizing TRalpha/c-ErbA and retinoic acid receptor activity.
- Cytoplasmic retention of v-ErbA suggests interference with intracellular signaling.
Purpose of the Study:
- To investigate the role of v-ErbA in modulating intracellular signaling pathways.
- To determine if v-ErbA confers resistance to TGF-beta.
- To identify signaling pathways regulated by v-ErbA in erythroid progenitors.
Main Methods:
- Analysis of v-ErbA's effect on TGF-beta signaling.
- Investigation of the mTOR/p70S6K pathway activation.
- Assessment of band3 gene expression in response to TGF-beta and v-ErbA.
Main Results:
- The transforming v-ErbA confers TGF-beta independency to chicken erythroid progenitors.
- v-ErbA induces activation of the mTOR/p70S6K pathway.
- Both TGF-beta and mTOR/p70S6K pathways regulate the expression of the v-ErbA target gene, band3.
Conclusions:
- v-ErbA modulates specific signaling pathways, including TGF-beta and mTOR/p70S6K.
- These pathway alterations lead to changes in band3 gene expression, contributing to cellular transformation.
- This is the first demonstration of v-ErbA's specific modulation of signaling pathways impacting transformation-related gene expression.
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