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Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insalia-like growth factor receptor in mammary tumor cells

Balãá, M.E. - Labriola, L. - Salatino, M. - Movsichoff, F. - Peters, G. - Charreau, E.H. - Elizalde, P.V.
   
Fecha:
2001
Tipo de documento: 
info:eu-repo/semantics/article
info:ar-repo/semantics/artículo
info:eu-repo/semantics/publishedVersion
Formato:
application/pdf
Temas:
ErbB receptors - Mammary tumorigenesis - Progestin - Type I insulin-like growth factor receptor - antisense oligodeoxynucleotide - gestagen - medroxyprogesterone acetate - messenger RNA - neu differentiation factor - oligomer - protein tyrosine kinase - somatomedin C receptor - animal cell - animal experiment - animal model - animal tissue - article - breast carcinogenesis - breast epithelium - breast tumor - cell proliferation - complex formation - confocal laser microscopy - controlled study - female - gene activation - mouse - nonhuman - oncogene neu - priority journal - protein localization - protein phosphorylation - protein protein interaction - signal transduction - Animals - Enzyme Activation - Epithelial Cells - Female - Macromolecular Substances - Mammary Neoplasms, Experimental - Medroxyprogesterone 17-Acetate - Mice - Mice, Inbred BALB C - Oligodeoxyribonucleotides, Antisense - Phosphorylation - Progesterone Congeners - Receptor Cross-Talk - Receptor, erbB-2 - Receptor, IGF Type 1 - Signal Transduction - Tumor Cells, Cultured - Tyrosine - Animalia - Mink cell focus-forming virus
Descripción:
The present study focused on interactions between signaling pathways activated by progestins and by type I and II receptor tyrosine kinases (RTKs) in mammary tumors. An experimental model in which the synthetic progestin medroxyprogesterone acetate (MPA) induced mammary adenocarcinomas in Balb/c mice was used. MPA-stimulated proliferation, both in vivo and in vitro, of progestin-dependent tumors induced up-regulation of ErbB-2 protein levels and tyrosine phosphorylation of this receptor. Combinations of antisense oligodeoxynueleotides (ASODNs) directed to ErbB-2 mRNA with ASODNs directed to the insulin-like growth factor-I receptor (IGF-IR) were used to study the effect of the simultaneous block of these receptors on the MPA-induced proliferation of epithelial cells from the progestin-dependent C4HD line. Neither synergistic nor additive effects on the inhibition of MPA-induced proliferation of C4HD cells were observed as a result of the combination of these ASODNs. Suppression of IGF-IR expression by ASODNs resulted in complete abrogation of MPA-induced phosphorylation of ErbB-2 in C4HD cells, whereas blockage of ErbB-2 did not affect IGF-IR phosphorylation. These results show the existence of a hierarchical interaction between IGF-IR and ErbB-2, by means of which IGF-IR directs ErbB-2 phosphorylation. We demonstrated, for the first time, that this hierarchical interaction involves physical association of both receptors, resulting in the formation of a heteromeric complex. Furthermore, confocal laser microscopy experiments demonstrated that MPA was able to induce co-localization of ErbB-2 and IGF-IR. This hetero-oligomer was also found in MCF-7 human breast cancer cells in which association of IGF-IR and ErbB-2 was induced by heregulin and IGF-I.
Fil:Labriola, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Salatino, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Movsichoff, F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Peters, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Charreau, E.H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Elizalde, P.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fuente:
Oncogene 2001;20(1):34-47
Identificador:
http://hdl.handle.net/20.500.12110/paper_09509232_v20_n1_p34_Balaa
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_09509232_v20_n1_p34_Balaa_oai
Derechos:
info:eu-repo/semantics/openAccess

Cita bibliográfica:

Balãá, M.E. ; Labriola, L. ; Salatino, M. ; et al. (2001).  Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insalia-like growth factor receptor in mammary tumor cells.  (info:eu-repo/semantics/article).  [consultado:  ] Disponible en el Repositorio Digital Institucional de la Universidad de Buenos Aires:  <http://hdl.handle.net/20.500.12110/paper_09509232_v20_n1_p34_Balaa>