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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Chick Embryo
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Chromones / pharmacology
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Culture Media
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Gene Expression Regulation / drug effects*
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Morpholines / pharmacology
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Oncogene Proteins v-erbA / physiology*
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Phosphorylation
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Protein Kinases / drug effects
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Ribosomal Protein S6 Kinases, 70-kDa / drug effects
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Ribosomal Protein S6 Kinases, 70-kDa / genetics
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Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
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Sirolimus / pharmacology
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Smad2 Protein / metabolism
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Smad3 Protein / metabolism
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TOR Serine-Threonine Kinases
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Transforming Growth Factor alpha / pharmacology*
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Transforming Growth Factor beta / physiology*
Substances
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Chromones
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Culture Media
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Morpholines
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Oncogene Proteins v-erbA
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Smad2 Protein
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Smad3 Protein
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Transforming Growth Factor alpha
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Transforming Growth Factor beta
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Protein Kinases
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Ribosomal Protein S6 Kinases, 70-kDa
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TOR Serine-Threonine Kinases
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Sirolimus