Document Detail


Etoposide induces apoptosis and upregulation of TACE/ADAM17 and ADAM10 in an in vitro male germ cell line model.
MedLine Citation:
PMID:  20800622     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Etoposide is a widely used anticancer drug in the treatment of different tumors. Etoposide is known to activate a wide range of intracellular signals, which may in turn induce cellular responses other than apoptosis. ADAM10 and TACE/ADAM17 belong to a family of transmembrane extracellular metalloproteinases involved in paracrine/juxtacrine regulation of many signaling pathways. The aim of this work was to evaluate if etoposide induces upregulation of ADAM10 or TACE/ADAM17 in two cell lines (GC-1 and GC-2) derived from male germ cells. Results showed that etoposide induced apoptosis in a dose-response manner in both GC-1 and GC-2 cells. Apoptosis started to increase 6h after etoposide addition in GC-2 cells, whereas the same was observed 18h after addition to the GC-1 cells. Protein and mRNA levels of ADAM10 and TACE/ADAM17 increased 18h after etoposide was removed from the GC-1 cells. In GC-2 cells, the protein levels of both proteins increased 12h after etoposide was removed. ADAM10 mRNA increased after 3h and then steadily decreased up to 12h after removal, whereas TACE/ADAM17 mRNA decreased after etoposide removal. Finally, apoptosis was prevented in GC-1 and GC-2 cells by the addition of pharmacological inhibitors of ADAM10 and TACE/ADAM17 to the culture medium of etoposide-treated cells. Our results show for the first time that etoposide upregulates ADAM10 and TACE/ADAM17 mRNA and protein levels. In addition, we also show that ADAM10 and TACE/ADAM17 have a role in etoposide-induced apoptosis.
Authors:
Carlos Lizama; Andreas Ludwig; Ricardo D Moreno
Publication Detail:
Type:  Journal Article     Date:  2010-08-25
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1813     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  120-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Departamento de Fisiología, Pontificia Universidad Católica de Chile, Santiago, Chile.
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