Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes

The high incidence of obesity-related pathologies, led to the study of the mechanisms involved in preadipose cell proliferation and differentiation. Here, we demonstrate that modulation of erbB2, plays a fundamental role during proliferation and adipogenic induction of preadipocytes. Using 3T3-L1 ce...

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Autores principales:	Pagano, Eleonora, Coso, Omar Adrian, Calvo, Juan Carlos
Publicado:	2008
Materias:	3T3-L1 Adipogenesis EGFR/erbB1 erbB2 Tyrphostin 2 (2 amino 3 methoxyphenyl)chromone 5 (2 benzothiazolyl)thiomethyl 4 hydroxy 3 methoxybenzylidenecyanoacetamide anthra[1,9 cd]pyrazol 6(2h) one dexamethasone epidermal growth factor epidermal growth factor receptor epidermal growth factor receptor 2 heterodimer isobutylmethylxanthine mitogen activated protein kinase mitogen activated protein kinase inhibitor mitogen activated protein kinase kinase mitogen activated protein kinase p38 protein tyrosine kinase protein tyrosine kinase inhibitor stress activated protein kinase stress activated protein kinase inhibitor tyrphostin tyrphostin ag 879 unclassified drug adipogenesis animal cell article cell differentiation cell proliferation cell strain 3T3 controlled study down regulation embryo functional proteomics inhibition kinetics mouse nonhuman priority journal proadipocyte protein expression protein function protein induction protein phosphorylation protein synthesis inhibition adipocyte animal cytology gene expression regulation genetics metabolism physiology 3T3-L1 Cells Adipocytes Animals Cell Differentiation Cell Proliferation Gene Expression Regulation Mice Mitogen-Activated Protein Kinases Receptor, Epidermal Growth Factor Receptor, erbB-2
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v104_n1_p274_Pagano http://hdl.handle.net/20.500.12110/paper_07302312_v104_n1_p274_Pagano
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_07302312_v104_n1_p274_Pagano
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spelling	paper:paper_07302312_v104_n1_p274_Pagano2023-06-08T15:43:43Z Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes Pagano, Eleonora Coso, Omar Adrian Calvo, Juan Carlos 3T3-L1 Adipogenesis EGFR/erbB1 erbB2 Tyrphostin 2 (2 amino 3 methoxyphenyl)chromone 5 (2 benzothiazolyl)thiomethyl 4 hydroxy 3 methoxybenzylidenecyanoacetamide anthra[1,9 cd]pyrazol 6(2h) one dexamethasone epidermal growth factor epidermal growth factor receptor epidermal growth factor receptor 2 heterodimer isobutylmethylxanthine mitogen activated protein kinase mitogen activated protein kinase inhibitor mitogen activated protein kinase kinase mitogen activated protein kinase p38 protein tyrosine kinase protein tyrosine kinase inhibitor stress activated protein kinase stress activated protein kinase inhibitor tyrphostin tyrphostin ag 879 unclassified drug epidermal growth factor receptor epidermal growth factor receptor 2 mitogen activated protein kinase adipogenesis animal cell article cell differentiation cell proliferation cell strain 3T3 controlled study down regulation embryo functional proteomics inhibition kinetics mouse nonhuman priority journal proadipocyte protein expression protein function protein induction protein phosphorylation protein synthesis inhibition adipocyte animal cytology gene expression regulation genetics metabolism physiology 3T3-L1 Cells Adipocytes Adipogenesis Animals Cell Differentiation Cell Proliferation Gene Expression Regulation Mice Mitogen-Activated Protein Kinases Receptor, Epidermal Growth Factor Receptor, erbB-2 The high incidence of obesity-related pathologies, led to the study of the mechanisms involved in preadipose cell proliferation and differentiation. Here, we demonstrate that modulation of erbB2, plays a fundamental role during proliferation and adipogenic induction of preadipocytes. Using 3T3-L1 cells as model, we demonstrate that EGF (10 nM, 5 min) in addition to stimulate receptor tyrosine phosphorylation of both erbB2 and EGFR, is able to induce the heterodimer erbB2-EGFR. We treated proliferating 3T3-L1 cells with two inhibitors, AG 825 (IC50 0.35 μM, 54 times more selective for erbB2 than for EGFR, IC50 19 μM), and AG 879 (IC50 of 1 μM for erbB2 versus 500 μM for EGFR). We found that both inhibited the proliferation on a dose-dependent basis, reaching a 30% maximal inhibition at 100 μM (P < 0.001) for AG825, and a 20% maximal inhibition at 10 μM (P < 0.001) for AG 879. These results involve erbB2 in 3T3-L1 proliferation. When studying the differentiation process, we found that the action of MIX-Dexa immediately activates MEK, JNK and p38 kinases. We observed that PD98059 and SP600125 (MEK-ERK and JNK inhibitors, respectively) added 1 h prior to the MIX-Dexa induction produced a decrease in erbB2 expression after 6 h, which is even greater than the one produced by the inducers, MIX-Dexa. This work supports erbB2 as a key factor in 3T3-L1 adipogenesis, acting mostly and not only during the proliferative phase but also during the differentiation through modulation of both its expression and activity. © 2007 Wiley-Liss, Inc. Fil:Pagano, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coso, O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Calvo, J.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2008 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v104_n1_p274_Pagano http://hdl.handle.net/20.500.12110/paper_07302312_v104_n1_p274_Pagano
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	3T3-L1 Adipogenesis EGFR/erbB1 erbB2 Tyrphostin 2 (2 amino 3 methoxyphenyl)chromone 5 (2 benzothiazolyl)thiomethyl 4 hydroxy 3 methoxybenzylidenecyanoacetamide anthra[1,9 cd]pyrazol 6(2h) one dexamethasone epidermal growth factor epidermal growth factor receptor epidermal growth factor receptor 2 heterodimer isobutylmethylxanthine mitogen activated protein kinase mitogen activated protein kinase inhibitor mitogen activated protein kinase kinase mitogen activated protein kinase p38 protein tyrosine kinase protein tyrosine kinase inhibitor stress activated protein kinase stress activated protein kinase inhibitor tyrphostin tyrphostin ag 879 unclassified drug epidermal growth factor receptor epidermal growth factor receptor 2 mitogen activated protein kinase adipogenesis animal cell article cell differentiation cell proliferation cell strain 3T3 controlled study down regulation embryo functional proteomics inhibition kinetics mouse nonhuman priority journal proadipocyte protein expression protein function protein induction protein phosphorylation protein synthesis inhibition adipocyte animal cytology gene expression regulation genetics metabolism physiology 3T3-L1 Cells Adipocytes Adipogenesis Animals Cell Differentiation Cell Proliferation Gene Expression Regulation Mice Mitogen-Activated Protein Kinases Receptor, Epidermal Growth Factor Receptor, erbB-2
spellingShingle	3T3-L1 Adipogenesis EGFR/erbB1 erbB2 Tyrphostin 2 (2 amino 3 methoxyphenyl)chromone 5 (2 benzothiazolyl)thiomethyl 4 hydroxy 3 methoxybenzylidenecyanoacetamide anthra[1,9 cd]pyrazol 6(2h) one dexamethasone epidermal growth factor epidermal growth factor receptor epidermal growth factor receptor 2 heterodimer isobutylmethylxanthine mitogen activated protein kinase mitogen activated protein kinase inhibitor mitogen activated protein kinase kinase mitogen activated protein kinase p38 protein tyrosine kinase protein tyrosine kinase inhibitor stress activated protein kinase stress activated protein kinase inhibitor tyrphostin tyrphostin ag 879 unclassified drug epidermal growth factor receptor epidermal growth factor receptor 2 mitogen activated protein kinase adipogenesis animal cell article cell differentiation cell proliferation cell strain 3T3 controlled study down regulation embryo functional proteomics inhibition kinetics mouse nonhuman priority journal proadipocyte protein expression protein function protein induction protein phosphorylation protein synthesis inhibition adipocyte animal cytology gene expression regulation genetics metabolism physiology 3T3-L1 Cells Adipocytes Adipogenesis Animals Cell Differentiation Cell Proliferation Gene Expression Regulation Mice Mitogen-Activated Protein Kinases Receptor, Epidermal Growth Factor Receptor, erbB-2 Pagano, Eleonora Coso, Omar Adrian Calvo, Juan Carlos Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes
topic_facet	3T3-L1 Adipogenesis EGFR/erbB1 erbB2 Tyrphostin 2 (2 amino 3 methoxyphenyl)chromone 5 (2 benzothiazolyl)thiomethyl 4 hydroxy 3 methoxybenzylidenecyanoacetamide anthra[1,9 cd]pyrazol 6(2h) one dexamethasone epidermal growth factor epidermal growth factor receptor epidermal growth factor receptor 2 heterodimer isobutylmethylxanthine mitogen activated protein kinase mitogen activated protein kinase inhibitor mitogen activated protein kinase kinase mitogen activated protein kinase p38 protein tyrosine kinase protein tyrosine kinase inhibitor stress activated protein kinase stress activated protein kinase inhibitor tyrphostin tyrphostin ag 879 unclassified drug epidermal growth factor receptor epidermal growth factor receptor 2 mitogen activated protein kinase adipogenesis animal cell article cell differentiation cell proliferation cell strain 3T3 controlled study down regulation embryo functional proteomics inhibition kinetics mouse nonhuman priority journal proadipocyte protein expression protein function protein induction protein phosphorylation protein synthesis inhibition adipocyte animal cytology gene expression regulation genetics metabolism physiology 3T3-L1 Cells Adipocytes Adipogenesis Animals Cell Differentiation Cell Proliferation Gene Expression Regulation Mice Mitogen-Activated Protein Kinases Receptor, Epidermal Growth Factor Receptor, erbB-2
description	The high incidence of obesity-related pathologies, led to the study of the mechanisms involved in preadipose cell proliferation and differentiation. Here, we demonstrate that modulation of erbB2, plays a fundamental role during proliferation and adipogenic induction of preadipocytes. Using 3T3-L1 cells as model, we demonstrate that EGF (10 nM, 5 min) in addition to stimulate receptor tyrosine phosphorylation of both erbB2 and EGFR, is able to induce the heterodimer erbB2-EGFR. We treated proliferating 3T3-L1 cells with two inhibitors, AG 825 (IC50 0.35 μM, 54 times more selective for erbB2 than for EGFR, IC50 19 μM), and AG 879 (IC50 of 1 μM for erbB2 versus 500 μM for EGFR). We found that both inhibited the proliferation on a dose-dependent basis, reaching a 30% maximal inhibition at 100 μM (P < 0.001) for AG825, and a 20% maximal inhibition at 10 μM (P < 0.001) for AG 879. These results involve erbB2 in 3T3-L1 proliferation. When studying the differentiation process, we found that the action of MIX-Dexa immediately activates MEK, JNK and p38 kinases. We observed that PD98059 and SP600125 (MEK-ERK and JNK inhibitors, respectively) added 1 h prior to the MIX-Dexa induction produced a decrease in erbB2 expression after 6 h, which is even greater than the one produced by the inducers, MIX-Dexa. This work supports erbB2 as a key factor in 3T3-L1 adipogenesis, acting mostly and not only during the proliferative phase but also during the differentiation through modulation of both its expression and activity. © 2007 Wiley-Liss, Inc.
author	Pagano, Eleonora Coso, Omar Adrian Calvo, Juan Carlos
author_facet	Pagano, Eleonora Coso, Omar Adrian Calvo, Juan Carlos
author_sort	Pagano, Eleonora
title	Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes
title_short	Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes
title_full	Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes
title_fullStr	Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes
title_full_unstemmed	Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes
title_sort	down-modulation of erbb2 activity is necessary but not enough in the differentiation of 3t3-l1 preadipocytes
publishDate	2008
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v104_n1_p274_Pagano http://hdl.handle.net/20.500.12110/paper_07302312_v104_n1_p274_Pagano
work_keys_str_mv	AT paganoeleonora downmodulationoferbb2activityisnecessarybutnotenoughinthedifferentiationof3t3l1preadipocytes AT cosoomaradrian downmodulationoferbb2activityisnecessarybutnotenoughinthedifferentiationof3t3l1preadipocytes AT calvojuancarlos downmodulationoferbb2activityisnecessarybutnotenoughinthedifferentiationof3t3l1preadipocytes
_version_	1768541942002483200

Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes

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