Artículo
Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insulin-like growth factor receptor in mammary tumor cells.
Balaña, Maria Eugenia
; Labriola, Leticia; Salatino, Mariana
; Movsichoff, Federico
; Peters, María Giselle
; Charreau, Eduardo Hernan
; Elizalde, Patricia Virginia






Fecha de publicación:
01/2001
Editorial:
Nature Publishing Group
Revista:
Oncogene
ISSN:
0950-9232
e-ISSN:
1476-5594
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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 oligodeoxynucleotides (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.
Palabras clave:
Erbb-2
,
Igf-Ir.
,
Mammary Tumor
,
Cancer
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Articulos(ICT - MILSTEIN) [174]
Articulos de INST.DE CS. Y TECNOLOGIA "DR. CESAR MILSTEIN"
Articulos de INST.DE CS. Y TECNOLOGIA "DR. CESAR MILSTEIN"
Articulos(IIBBA) [1078]
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos(OCA HOUSSAY) [2204]
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos(IBYME) [1500]
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
Balaña, Maria Eugenia; Labriola, Leticia; Salatino, Mariana; Movsichoff, Federico; Peters, María Giselle; et al.; Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insulin-like growth factor receptor in mammary tumor cells.; Nature Publishing Group; Oncogene; 20; 1; 1-2001; 34-47
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