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Cell Growth & Differentiation, Vol 7, Issue 9 1251-1259, Copyright © 1996 by American Association of Cancer Research


ARTICLES

p21ras induced differentiation-related gene expression in fetal brown adipocyte primary cells and cell lines

M Lorenzo, AM Valverde, T Teruel, A Alvarez and M Benito
Departamento de Bioquimica y Biologia Molecular, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.

Transfection of primary rat fetal brown adipocytes with constructs of SV40 large T antigen, alone and together with lys12-mutated H-ras gene, gave permanent cell lines showing an immortalized or transformed phenotype, respectively, all of them selected by the expression of the uncoupling protein (UCP), a tissue-specific marker. Primary brown adipocytes and immortalized cell lines respond to insulin-like growth factor I (IGF-I) by increasing their lipid content and the mRNA expression of both the adipogenic marker fatty acid synthase (FAS) and the thermogenic marker UCP. IGF-I-induced differentiation-related gene expression at 24 h in both primary and immortalized brown adipocytes was mediated by an increase in p21ras.GTP active protein content. Transformed cell lines overexpressing exogenous p21ras (mainly in its ras.GTP active form) constitutively showed a higher lipid content and a higher FAS and UCP mRNA expression compared to primary and immortalized cells. These transformed cells were IGF-I independent with respect to their studied differentiation-related parameters. Additionally, transient transfection of primary brown adipocytes with the transforming ras gene induced UCP and FAS mRNA expression as well as cotransactivated UCP-chloramphenicol acetyltransferase fusion gene. Moreover, IGF-I transactivation of UCP promoter was partially precluded by cotransfection with the dominant-negative ras gene. Our results strongly suggest that IGF-I/p21ras induces adipogenic- and thermogenic-related gene expression in brown adipocytes.


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J Biol ChemHome page
T. Teruel, R. Hernandez, M. Benito, and M. Lorenzo
Rosiglitazone and Retinoic Acid Induce Uncoupling Protein-1 (UCP-1) in a p38 Mitogen-activated Protein Kinase-dependent Manner in Fetal Primary Brown Adipocytes
J. Biol. Chem., January 3, 2003; 278(1): 263 - 269.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
P. Navarro, A. M. Valverde, M. Benito, and M. Lorenzo
Activated Ha-ras Induces Apoptosis by Association with Phosphorylated Bcl-2 in a Mitogen-activated Protein Kinase-independent Manner
J. Biol. Chem., July 2, 1999; 274(27): 18857 - 18863.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1996 by the American Association of Cancer Research.