Involvement of the TGF-beta and mTOR/p70S6Kinase pathways in the transformation process induced by v-ErbA.
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.
Université de Lyon, Lyon, France. gonin@cgmc.univ-lyon1.fr
S
S
Gonin-Giraud
C
C
Bresson-Mazet
O
O
Gandrillon
D000818:Animals; D002642:Chick Embryo; D002867:Chromones / Q000494:pharmacology; D003470:Culture Media; D005786:Gene Expression Regulation / Q000187:drug effects*; D009025:Morpholines / Q000494:pharmacology; D018774:Oncogene Proteins v-erbA / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D002867:Chromones; D003470:Culture Media; D009025:Morpholines; D018774:Oncogene Proteins v-erbA; D051899:Smad2 Protein; D051900:Smad3 Protein; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011494:Protein Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus