| Cellular senescence of human mammary epithelial cells (HMEC) is associated with an altered MMP-7/HB-EGF signaling and increased formation of elastin-like structures. | |
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MedLine Citation:
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PMID: 19682489 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The extracellular matrix (ECM) and a complex interplay of cell-to-cell and cell-to-matrix (ECM) interactions provide important platforms to determine cellular senescence and a potentially tumorigenic transformation of normal human mammary epithelial cells (HMEC). An enhanced formation of extracellular filaments, consisting of elastin-like structures, in senescent post-selection HMEC populations was paralleled by a significantly increased expression of its precursor protein tropoelastin and matched with a markedly elevated activity of the cross-linking enzyme family of lysyl oxidases (LOX). RNAi experiments revealed both the ECM metalloproteinase MMP-7 and the growth factor HB-EGF as potential effectors of an increased tropoelastin expression. Moreover, co-localization of MMP-7 and HB-EGF as well as a concomittant downstream signaling via Fra-1 indicated a possible association between the reduced MMP-7 enzyme activity and an impaired HB-EGF processing, resulting in an enhanced tropoelastin synthesis during senescence of HMEC. In agreement with previous work, these findings suggested an important influence of the extracellular proteinase MMP-7 on the aging process of HMEC, affecting both extracellular remodeling as well as intracellular signaling pathways. |
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Authors:
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Catharina Bertram; Ralf Hass |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-08-12 |
Journal Detail:
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Title: Mechanisms of ageing and development Volume: 130 ISSN: 1872-6216 ISO Abbreviation: Mech. Ageing Dev. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-05 Completed Date: 2009-12-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0347227 Medline TA: Mech Ageing Dev Country: Ireland |
Other Details:
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Languages: eng Pagination: 657-69 Citation Subset: IM |
Affiliation:
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Clinic of Obstetrics and Gynecology, Biochemistry and Tumor Biology Lab (OE6411), Medical School, D - 30625 Hannover, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Aging* Cell Transformation, Neoplastic / metabolism Cells, Cultured Cyclin-Dependent Kinase Inhibitor p16 / metabolism Elastin / metabolism* Epithelial Cells / enzymology* Female Humans Intercellular Signaling Peptides and Proteins / genetics, metabolism* Mammary Glands, Human / cytology, enzymology* Matrix Metalloproteinase 7 / genetics, metabolism* Middle Aged Protein-Lysine 6-Oxidase / metabolism Proto-Oncogene Proteins c-fos / metabolism RNA Interference Signal Transduction* / genetics Time Factors Tropoelastin / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p16; 0/Intercellular Signaling Peptides and Proteins; 0/Proto-Oncogene Proteins c-fos; 0/Tropoelastin; 0/fos-related antigen 1; 149176-25-0/heparin-binding EGF-like growth factor; 9007-58-3/Elastin; EC 1.4.3.13/Protein-Lysine 6-Oxidase; EC 3.4.24.23/MMP7 protein, human; EC 3.4.24.23/Matrix Metalloproteinase 7 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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