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Apoptosis is the predominant process controlling cell deletion during post-lactational mammary gland remodeling. The members of the Bcl-2 protein family, whose expression levels are under the control of lactogenic hormones, internally control this mechanism. Epidermal growth factor (EGF) belongs to a family of proteins that act as survival factors for mammary epithelial cells upon binding to specific membrane tyrosine kinase receptors. Expression of EGF peaks during lactation and dramatically decreases in the involuting mammary gland. Though it was suggested that the protective effect of EGF is mediated through the phosphatidylinositol-3-kinase (PI3K) or MEK/ERK kinases activities, little is known about the downstream mechanisms involved on the anti-apoptotic effect of EGF on mammary epithelial cells; particularly the identity of target genes controlling apoptosis. Here, we focused on the effect of EGF on the survival of mammary epithelial cells. We particularly aimed at the characterization of the signaling pathways that were triggered by this growth factor, impinge upon expression of Bcl-2 family members and therefore have an impact on the regulation of cell survival. We demonstrate that EGF provokes the induction of the anti-apoptotic isoform Bcl-XL and the phosphorylation and down-regulation of the pro-apoptotic protein Bad. The activation of JNK and PI3K/AKT signaling pathways promotes the induction of Bcl-XL while AKT activation also leads to Bad phosphorylation and down-regulation. This protective effect of EGF correlates mainly with the up-regulation of Bcl-XL than with the down-regulation of Bad. In fact, HC11 cells unable to express bcl-X, die even in the presence of EGF. In this context, Bcl-XL emerges as a key anti-apoptotic molecule critical for mediating EGF cell survival. © 2008 Elsevier B.V. All rights reserved.


Documento: Artículo
Título:Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells
Autor:Romorini, L.; Coso, O.A.; Pecci, A.
Filiación:Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina
Departamento de Fisiología, Biología Molecular y Celular, Universidad de Buenos Aires, Buenos Aires, Argentina
IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Apoptosis; Bad; Bcl-XL; EGF; Mammary epithelial cell; MAPKs; cytochrome c; mitogen activated protein kinase 1; mitogen activated protein kinase 3; phosphatidylinositol 3 kinase; protein BAD; protein bcl 2; protein bcl xl; protein kinase B; recombinant epidermal growth factor; stress activated protein kinase; cytochrome c; epidermal growth factor; phosphatidylinositol 3 kinase; protein BAD; protein bcl x; protein kinase B; stress activated protein kinase; animal cell; apoptosis; article; breast epithelium; cell survival; controlled study; down regulation; enzyme activation; epithelium cell; mitochondrion; mouse; nonhuman; priority journal; protein expression; protein family; protein induction; protein phosphorylation; protein secretion; signal transduction; animal; cell survival; epithelium cell; female; genetics; human; metabolism; phosphorylation; udder; 1-Phosphatidylinositol 3-Kinase; Animals; Apoptosis; bcl-Associated Death Protein; bcl-X Protein; Cell Survival; Cytochromes c; Down-Regulation; Epidermal Growth Factor; Epithelial Cells; Female; Humans; JNK Mitogen-Activated Protein Kinases; Mammary Glands, Animal; Mice; Mitochondria; Phosphorylation; Proto-Oncogene Proteins c-akt
Página de inicio:496
Página de fin:505
Título revista:Biochimica et Biophysica Acta - Molecular Cell Research
Título revista abreviado:Biochim. Biophys. Acta Mol. Cell Res.
CAS:cytochrome c, 9007-43-6, 9064-84-0; mitogen activated protein kinase 1, 137632-08-7; mitogen activated protein kinase 3, 137632-07-6; phosphatidylinositol 3 kinase, 115926-52-8; protein bcl 2, 219306-68-0; protein bcl xl, 151033-38-4; protein kinase B, 148640-14-6; stress activated protein kinase, 155215-87-5; epidermal growth factor, 62229-50-9; 1-Phosphatidylinositol 3-Kinase,; Cytochromes c, 9007-43-6; Epidermal Growth Factor, 62229-50-9; JNK Mitogen-Activated Protein Kinases,; Proto-Oncogene Proteins c-akt,; bcl-Associated Death Protein; bcl-X Protein


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---------- APA ----------
Romorini, L., Coso, O.A. & Pecci, A. (2009) . Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells. Biochimica et Biophysica Acta - Molecular Cell Research, 1793(3), 496-505.
---------- CHICAGO ----------
Romorini, L., Coso, O.A., Pecci, A. "Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells" . Biochimica et Biophysica Acta - Molecular Cell Research 1793, no. 3 (2009) : 496-505.
---------- MLA ----------
Romorini, L., Coso, O.A., Pecci, A. "Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells" . Biochimica et Biophysica Acta - Molecular Cell Research, vol. 1793, no. 3, 2009, pp. 496-505.
---------- VANCOUVER ----------
Romorini, L., Coso, O.A., Pecci, A. Bcl-XL mediates epidermal growth factor dependent cell survival in HC11 mammary epithelial cells. Biochim. Biophys. Acta Mol. Cell Res. 2009;1793(3):496-505.