Cargando…

Extracellular Matrix Regulates Apoptosis in Mammary Epithelium through a Control on Insulin Signaling

Adherent epithelial cells require interactions with the extracellular matrix for their survival, though the mechanism is ill-defined. In long term cultures of primary mammary epithelial cells, a laminin-rich basement membrane (BM) but not collagen I suppresses apoptosis, indicating that adhesion sur...

Descripción completa

Detalles Bibliográficos
Autores principales: Farrelly, Nadia, Lee, Yi-Ju, Oliver, Janine, Dive, Caroline, Streuli, Charles H.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150575/
https://www.ncbi.nlm.nih.gov/pubmed/10087274
_version_ 1782144628214988800
author Farrelly, Nadia
Lee, Yi-Ju
Oliver, Janine
Dive, Caroline
Streuli, Charles H.
author_facet Farrelly, Nadia
Lee, Yi-Ju
Oliver, Janine
Dive, Caroline
Streuli, Charles H.
author_sort Farrelly, Nadia
collection PubMed
description Adherent epithelial cells require interactions with the extracellular matrix for their survival, though the mechanism is ill-defined. In long term cultures of primary mammary epithelial cells, a laminin-rich basement membrane (BM) but not collagen I suppresses apoptosis, indicating that adhesion survival signals are specific in their response (Pullan et al. 1996. J. Cell Sci. 109:631–642). We now demonstrate that the signal from BM is mediated by integrins and requires both the α6 and β1 subunits. In addition, a hormonal signal from insulin or insulin-like growth factors, but not hydrocortisone or prolactin, is necessary to suppress mammary cell apoptosis, indicating that BM and soluble factors cooperate in survival signaling. Insulin induced autophosphorylation of its receptor whether mammary cells were cultured on collagen I or BM substrata. However, both the tyrosine phosphorylation of insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase were enhanced in cells cultured on BM, as was the phosphorylation of the phosphatidylinositol 3-kinase effector, protein kinase B. These results suggest a novel extracellular matrix–dependent restriction point in insulin signaling in mammary epithelial cells. The proximal signal transduction event of insulin receptor phosphorylation is not dependent on extracellular matrix, but the activation of downstream effectors requires adhesion to BM. Since phosphatidylinositol 3-kinase was required for mammary epithelial cell survival, we propose that a possible mechanism for BM-mediated suppression of apoptosis is through its facilitative effects on insulin signaling.
format Text
id pubmed-2150575
institution National Center for Biotechnology Information
language English
publishDate 1999
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21505752008-05-01 Extracellular Matrix Regulates Apoptosis in Mammary Epithelium through a Control on Insulin Signaling Farrelly, Nadia Lee, Yi-Ju Oliver, Janine Dive, Caroline Streuli, Charles H. J Cell Biol Regular Articles Adherent epithelial cells require interactions with the extracellular matrix for their survival, though the mechanism is ill-defined. In long term cultures of primary mammary epithelial cells, a laminin-rich basement membrane (BM) but not collagen I suppresses apoptosis, indicating that adhesion survival signals are specific in their response (Pullan et al. 1996. J. Cell Sci. 109:631–642). We now demonstrate that the signal from BM is mediated by integrins and requires both the α6 and β1 subunits. In addition, a hormonal signal from insulin or insulin-like growth factors, but not hydrocortisone or prolactin, is necessary to suppress mammary cell apoptosis, indicating that BM and soluble factors cooperate in survival signaling. Insulin induced autophosphorylation of its receptor whether mammary cells were cultured on collagen I or BM substrata. However, both the tyrosine phosphorylation of insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase were enhanced in cells cultured on BM, as was the phosphorylation of the phosphatidylinositol 3-kinase effector, protein kinase B. These results suggest a novel extracellular matrix–dependent restriction point in insulin signaling in mammary epithelial cells. The proximal signal transduction event of insulin receptor phosphorylation is not dependent on extracellular matrix, but the activation of downstream effectors requires adhesion to BM. Since phosphatidylinositol 3-kinase was required for mammary epithelial cell survival, we propose that a possible mechanism for BM-mediated suppression of apoptosis is through its facilitative effects on insulin signaling. The Rockefeller University Press 1999-03-22 /pmc/articles/PMC2150575/ /pubmed/10087274 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Regular Articles
Farrelly, Nadia
Lee, Yi-Ju
Oliver, Janine
Dive, Caroline
Streuli, Charles H.
Extracellular Matrix Regulates Apoptosis in Mammary Epithelium through a Control on Insulin Signaling
title Extracellular Matrix Regulates Apoptosis in Mammary Epithelium through a Control on Insulin Signaling
title_full Extracellular Matrix Regulates Apoptosis in Mammary Epithelium through a Control on Insulin Signaling
title_fullStr Extracellular Matrix Regulates Apoptosis in Mammary Epithelium through a Control on Insulin Signaling
title_full_unstemmed Extracellular Matrix Regulates Apoptosis in Mammary Epithelium through a Control on Insulin Signaling
title_short Extracellular Matrix Regulates Apoptosis in Mammary Epithelium through a Control on Insulin Signaling
title_sort extracellular matrix regulates apoptosis in mammary epithelium through a control on insulin signaling
topic Regular Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150575/
https://www.ncbi.nlm.nih.gov/pubmed/10087274
work_keys_str_mv AT farrellynadia extracellularmatrixregulatesapoptosisinmammaryepitheliumthroughacontroloninsulinsignaling
AT leeyiju extracellularmatrixregulatesapoptosisinmammaryepitheliumthroughacontroloninsulinsignaling
AT oliverjanine extracellularmatrixregulatesapoptosisinmammaryepitheliumthroughacontroloninsulinsignaling
AT divecaroline extracellularmatrixregulatesapoptosisinmammaryepitheliumthroughacontroloninsulinsignaling
AT streulicharlesh extracellularmatrixregulatesapoptosisinmammaryepitheliumthroughacontroloninsulinsignaling