Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insalia-like growth factor receptor in mammary tumor cells
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 mic...
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2001
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v20_n1_p34_Balaa http://hdl.handle.net/20.500.12110/paper_09509232_v20_n1_p34_Balaa |
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paper:paper_09509232_v20_n1_p34_Balaa2023-06-08T15:54:48Z Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insalia-like growth factor receptor in mammary tumor cells Labriola, Leticia Salatino, Mariana Movsichoff, Federico Peters, María Giselle Charreau, Eduardo Hernán Elizalde, Patricia Virginia 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 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. 2001 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v20_n1_p34_Balaa http://hdl.handle.net/20.500.12110/paper_09509232_v20_n1_p34_Balaa |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Labriola, Leticia Salatino, Mariana Movsichoff, Federico Peters, María Giselle Charreau, Eduardo Hernán Elizalde, Patricia Virginia Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insalia-like growth factor receptor in mammary tumor cells |
| topic_facet |
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 |
| description |
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. |
| author |
Labriola, Leticia Salatino, Mariana Movsichoff, Federico Peters, María Giselle Charreau, Eduardo Hernán Elizalde, Patricia Virginia |
| author_facet |
Labriola, Leticia Salatino, Mariana Movsichoff, Federico Peters, María Giselle Charreau, Eduardo Hernán Elizalde, Patricia Virginia |
| author_sort |
Labriola, Leticia |
| title |
Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insalia-like growth factor receptor in mammary tumor cells |
| title_short |
Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insalia-like growth factor receptor in mammary tumor cells |
| title_full |
Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insalia-like growth factor receptor in mammary tumor cells |
| title_fullStr |
Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insalia-like growth factor receptor in mammary tumor cells |
| title_full_unstemmed |
Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insalia-like growth factor receptor in mammary tumor cells |
| title_sort |
activation of erbb-2 via a hierarchical interaction between erbb-2 and type i insalia-like growth factor receptor in mammary tumor cells |
| publishDate |
2001 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v20_n1_p34_Balaa http://hdl.handle.net/20.500.12110/paper_09509232_v20_n1_p34_Balaa |
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