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Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells
Inability to die by apoptosis is one of the reasons for the deregulated growth of tumour cells and the frequently observed failure of chemotherapy. In this study we thought to identify the common and functionally important characteristics responsible for the apoptosis resistance of pancreatic tumour...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2003
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394395/ https://www.ncbi.nlm.nih.gov/pubmed/14583775 http://dx.doi.org/10.1038/sj.bjc.6601330 |
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author | Trauzold, A Schmiedel, S Röder, C Tams, C Christgen, M Oestern, S Arlt, A Westphal, S Kapischke, M Ungefroren, H Kalthoff, H |
author_facet | Trauzold, A Schmiedel, S Röder, C Tams, C Christgen, M Oestern, S Arlt, A Westphal, S Kapischke, M Ungefroren, H Kalthoff, H |
author_sort | Trauzold, A |
collection | PubMed |
description | Inability to die by apoptosis is one of the reasons for the deregulated growth of tumour cells and the frequently observed failure of chemotherapy. In this study we thought to identify the common and functionally important characteristics responsible for the apoptosis resistance of pancreatic tumour cells. We analysed cell surface expression level of death receptors CD95 and TRAIL-R1-4 as well as the expression profile of sixteen apoptosis-relevant proteins in five pancreatic carcinoma cell lines Capan1, Colo357, PancTuI, Panc89 and Panc1. These data were evaluated in the context of sensitivity towards anti-CD95 and TRAIL-mediated apoptosis. Here we report that except for resistant Panc1 cells, which only marginally expressed CD95, all other cell lines showed comparable levels of CD95 and TRAIL receptors irrespectively of their apoptotic phenotype. Interestingly, we found that the elevated expression of FLIP, Bcl-x(L) and IAP in parallel with a downregulation of FADD and Bid was common for the resistant cell lines. Consequently, stable overexpression of XIAP, Bcl-x(L) or dominant negative FADD in sensitive cells significantly reduced the death receptor mediated apoptosis while the overexpression of Bid rendered the resistant cells sensitive. |
format | Text |
id | pubmed-2394395 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23943952009-09-10 Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells Trauzold, A Schmiedel, S Röder, C Tams, C Christgen, M Oestern, S Arlt, A Westphal, S Kapischke, M Ungefroren, H Kalthoff, H Br J Cancer Molecular and Cellular Pathology Inability to die by apoptosis is one of the reasons for the deregulated growth of tumour cells and the frequently observed failure of chemotherapy. In this study we thought to identify the common and functionally important characteristics responsible for the apoptosis resistance of pancreatic tumour cells. We analysed cell surface expression level of death receptors CD95 and TRAIL-R1-4 as well as the expression profile of sixteen apoptosis-relevant proteins in five pancreatic carcinoma cell lines Capan1, Colo357, PancTuI, Panc89 and Panc1. These data were evaluated in the context of sensitivity towards anti-CD95 and TRAIL-mediated apoptosis. Here we report that except for resistant Panc1 cells, which only marginally expressed CD95, all other cell lines showed comparable levels of CD95 and TRAIL receptors irrespectively of their apoptotic phenotype. Interestingly, we found that the elevated expression of FLIP, Bcl-x(L) and IAP in parallel with a downregulation of FADD and Bid was common for the resistant cell lines. Consequently, stable overexpression of XIAP, Bcl-x(L) or dominant negative FADD in sensitive cells significantly reduced the death receptor mediated apoptosis while the overexpression of Bid rendered the resistant cells sensitive. Nature Publishing Group 2003-11-03 2003-10-28 /pmc/articles/PMC2394395/ /pubmed/14583775 http://dx.doi.org/10.1038/sj.bjc.6601330 Text en Copyright © 2003 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Molecular and Cellular Pathology Trauzold, A Schmiedel, S Röder, C Tams, C Christgen, M Oestern, S Arlt, A Westphal, S Kapischke, M Ungefroren, H Kalthoff, H Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells |
title | Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells |
title_full | Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells |
title_fullStr | Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells |
title_full_unstemmed | Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells |
title_short | Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells |
title_sort | multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells |
topic | Molecular and Cellular Pathology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394395/ https://www.ncbi.nlm.nih.gov/pubmed/14583775 http://dx.doi.org/10.1038/sj.bjc.6601330 |
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