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The Combination of TRAIL Treatment and Cancer Cell Selective Expression of TRAIL-Death Receptor DR4 Induces Cell Death in TRAIL-Resistant Cancer Cells

The human telomerase reverse transcriptase (hTERT) promoter can be used for the tumor-specific expression of transgenes in order to induce selective cancer cell death. The hTERT core promoter is active in cancer cells but not in normal cells. To examine whether the combination of TNF-related apoptos...

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Autores principales: Choi, Eunah, Kim, Youngtae, Kim, Kunhong
Formato: Texto
Lenguaje:English
Publicado: Yonsei University College of Medicine 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687581/
https://www.ncbi.nlm.nih.gov/pubmed/16502485
http://dx.doi.org/10.3349/ymj.2006.47.1.55
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author Choi, Eunah
Kim, Youngtae
Kim, Kunhong
author_facet Choi, Eunah
Kim, Youngtae
Kim, Kunhong
author_sort Choi, Eunah
collection PubMed
description The human telomerase reverse transcriptase (hTERT) promoter can be used for the tumor-specific expression of transgenes in order to induce selective cancer cell death. The hTERT core promoter is active in cancer cells but not in normal cells. To examine whether the combination of TNF-related apoptosis inducing ligand (TRAIL) treatment and cancer cell-selective expression of the TRAIL-death receptor could induce cell death in TRAIL-resistant cancer cells, we generated a death receptor-4 (DR4)-expressing adenovirus (Ad-hTERT-DR4), in which the expression of DR4 is driven by the hTERT promoter. Upon infection, DR4 expression was slightly increased in cancer cell lines, and cell death was observed in TRAIL-resistant cancer cell lines but not in normal human cells when DR4 infection was combined with TRAIL treatment. We also generated an adenovirus that expresses a secretable isoleucine zipper (ILZ)-fused, extracellular portion of TRAIL (Ad-ILZ-TRAIL). In cells infected with Ad-ILZ-TRAIL, TRAIL was expressed, secreted, oligomerized and biologically active in the induction of apoptosis in TRAIL-sensitive cancer cells. When Ad-hTERT-DR4 infected TRAIL-resistant HCE4 cells and Ad-ILZ-TRAIL infected TRAIL-resistant HCE7 cells were co-cultured, cell deaths were evident 24 h after co-culture. Taken together, our results reveal that the combination of TRAIL and cancer cell-specific expression of DR4 has the potential to overcome the resistance of cancer cells to TRAIL without inducing significant cell death in normal cells.
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spelling pubmed-26875812009-06-04 The Combination of TRAIL Treatment and Cancer Cell Selective Expression of TRAIL-Death Receptor DR4 Induces Cell Death in TRAIL-Resistant Cancer Cells Choi, Eunah Kim, Youngtae Kim, Kunhong Yonsei Med J Original Article The human telomerase reverse transcriptase (hTERT) promoter can be used for the tumor-specific expression of transgenes in order to induce selective cancer cell death. The hTERT core promoter is active in cancer cells but not in normal cells. To examine whether the combination of TNF-related apoptosis inducing ligand (TRAIL) treatment and cancer cell-selective expression of the TRAIL-death receptor could induce cell death in TRAIL-resistant cancer cells, we generated a death receptor-4 (DR4)-expressing adenovirus (Ad-hTERT-DR4), in which the expression of DR4 is driven by the hTERT promoter. Upon infection, DR4 expression was slightly increased in cancer cell lines, and cell death was observed in TRAIL-resistant cancer cell lines but not in normal human cells when DR4 infection was combined with TRAIL treatment. We also generated an adenovirus that expresses a secretable isoleucine zipper (ILZ)-fused, extracellular portion of TRAIL (Ad-ILZ-TRAIL). In cells infected with Ad-ILZ-TRAIL, TRAIL was expressed, secreted, oligomerized and biologically active in the induction of apoptosis in TRAIL-sensitive cancer cells. When Ad-hTERT-DR4 infected TRAIL-resistant HCE4 cells and Ad-ILZ-TRAIL infected TRAIL-resistant HCE7 cells were co-cultured, cell deaths were evident 24 h after co-culture. Taken together, our results reveal that the combination of TRAIL and cancer cell-specific expression of DR4 has the potential to overcome the resistance of cancer cells to TRAIL without inducing significant cell death in normal cells. Yonsei University College of Medicine 2006-02-28 2006-02-28 /pmc/articles/PMC2687581/ /pubmed/16502485 http://dx.doi.org/10.3349/ymj.2006.47.1.55 Text en Copyright © 2006 The Yonsei University College of Medicine http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Choi, Eunah
Kim, Youngtae
Kim, Kunhong
The Combination of TRAIL Treatment and Cancer Cell Selective Expression of TRAIL-Death Receptor DR4 Induces Cell Death in TRAIL-Resistant Cancer Cells
title The Combination of TRAIL Treatment and Cancer Cell Selective Expression of TRAIL-Death Receptor DR4 Induces Cell Death in TRAIL-Resistant Cancer Cells
title_full The Combination of TRAIL Treatment and Cancer Cell Selective Expression of TRAIL-Death Receptor DR4 Induces Cell Death in TRAIL-Resistant Cancer Cells
title_fullStr The Combination of TRAIL Treatment and Cancer Cell Selective Expression of TRAIL-Death Receptor DR4 Induces Cell Death in TRAIL-Resistant Cancer Cells
title_full_unstemmed The Combination of TRAIL Treatment and Cancer Cell Selective Expression of TRAIL-Death Receptor DR4 Induces Cell Death in TRAIL-Resistant Cancer Cells
title_short The Combination of TRAIL Treatment and Cancer Cell Selective Expression of TRAIL-Death Receptor DR4 Induces Cell Death in TRAIL-Resistant Cancer Cells
title_sort combination of trail treatment and cancer cell selective expression of trail-death receptor dr4 induces cell death in trail-resistant cancer cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687581/
https://www.ncbi.nlm.nih.gov/pubmed/16502485
http://dx.doi.org/10.3349/ymj.2006.47.1.55
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