Involvement of the TGF-β and mTOR/p70S6Kinase pathways in the transformation process induced by v-ErbA

Abstract v-ErbA is the oncogenic form of TRα/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 TRα/c-ErbA and retinoic acid receptors. Neverthel...

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Bibliographic Details
Published in:Leukemia research 2008-12, Vol.32 (12), p.1878-1888
Main Authors: Gonin-Giraud, S, Bresson-Mazet, C, Gandrillon, O
Format: Article
Language:English
Subjects:
Animals
band3
Cellular Biology
Chick Embryo
Chromones - pharmacology
Culture Media
Erythroleukemia
Gene Expression Regulation - drug effects
Hematology, Oncology and Palliative Medicine
Life Sciences
Morpholines - pharmacology
mTOR/p70S6K
Oncogene Proteins v-erbA - physiology
Phosphorylation
Protein Kinases - drug effects
Protein Kinases - genetics
Protein Kinases - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Ribosomal Protein S6 Kinases, 70-kDa - drug effects
Ribosomal Protein S6 Kinases, 70-kDa - genetics
Ribosomal Protein S6 Kinases, 70-kDa - metabolism
Sirolimus - pharmacology
Smad2 Protein - metabolism
Smad3 Protein - metabolism
TGF-β
TOR Serine-Threonine Kinases
Transforming Growth Factor alpha - pharmacology
Transforming Growth Factor beta - physiology
v-ErbA
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Summary:Abstract v-ErbA is the oncogenic form of TRα/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 TRα/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-β independency and induces an activation of the mTOR/p70S6K pathway. In these cells, TGF-β 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.
ISSN:0145-2126
1873-5835
0145-2126
DOI:10.1016/j.leukres.2008.05.010