Tags

Type your tag names separated by a space and hit enter

Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
Cancer Gene Ther. 2004 Oct; 11(10):691-8.CG

Abstract

Breast cancer cells are generally resistant to induction of apoptosis by treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we demonstrate that both TRAIL-sensitive and TRAIL-resistant breast cancer cell lines can be efficiently killed by overexpression of the TRAIL receptor, death receptor 4 (DR4). The extent of cell death depended on the strength of the promoter driving DR4 expression. When driven by the strong CMV promoter, expression of DR4 killed over 90% of cells in five out of six cell lines tested in the absence of exogenous TRAIL. When driven by the relatively weak tumor-specific hTERT promoter, DR4 was less effective alone, but sensitized cells to killing by TRAIL. The extent of TRAIL sensitization depended on the magnitude of hTERT promoter activity. MCF-7 cells were relatively resistant to the action of DR4. We compared expression of the genes involved in transduction and execution of the death receptor-initiated apoptotic stimuli between MCF-7 and DR4-sensitive cell lines. We confirmed that in the panel of cell lines, MCF-7 was the only line deficient in expression of caspase 3. Bcl-2 and FLIP proteins, implicated in suppression of TRAIL-induced apoptosis, were expressed at a higher level.

Authors+Show Affiliations

Department of Medicine, Division of Medical Oncology, University of Texas Health Science Center at San Antonio, Texas, USA. kazhdan@uthscsa.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15354201

Citation

Kazhdan, Irene, and Robert A. Marciniak. "Death Receptor 4 (DR4) Efficiently Kills Breast Cancer Cells Irrespective of Their Sensitivity to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)." Cancer Gene Therapy, vol. 11, no. 10, 2004, pp. 691-8.
Kazhdan I, Marciniak RA. Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Cancer Gene Ther. 2004;11(10):691-8.
Kazhdan, I., & Marciniak, R. A. (2004). Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Cancer Gene Therapy, 11(10), 691-8.
Kazhdan I, Marciniak RA. Death Receptor 4 (DR4) Efficiently Kills Breast Cancer Cells Irrespective of Their Sensitivity to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL). Cancer Gene Ther. 2004;11(10):691-8. PubMed PMID: 15354201.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). AU - Kazhdan,Irene, AU - Marciniak,Robert A, PY - 2004/9/9/pubmed PY - 2005/3/18/medline PY - 2004/9/9/entrez SP - 691 EP - 8 JF - Cancer gene therapy JO - Cancer Gene Ther VL - 11 IS - 10 N2 - Breast cancer cells are generally resistant to induction of apoptosis by treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we demonstrate that both TRAIL-sensitive and TRAIL-resistant breast cancer cell lines can be efficiently killed by overexpression of the TRAIL receptor, death receptor 4 (DR4). The extent of cell death depended on the strength of the promoter driving DR4 expression. When driven by the strong CMV promoter, expression of DR4 killed over 90% of cells in five out of six cell lines tested in the absence of exogenous TRAIL. When driven by the relatively weak tumor-specific hTERT promoter, DR4 was less effective alone, but sensitized cells to killing by TRAIL. The extent of TRAIL sensitization depended on the magnitude of hTERT promoter activity. MCF-7 cells were relatively resistant to the action of DR4. We compared expression of the genes involved in transduction and execution of the death receptor-initiated apoptotic stimuli between MCF-7 and DR4-sensitive cell lines. We confirmed that in the panel of cell lines, MCF-7 was the only line deficient in expression of caspase 3. Bcl-2 and FLIP proteins, implicated in suppression of TRAIL-induced apoptosis, were expressed at a higher level. SN - 0929-1903 UR - https://www.unboundmedicine.com/medline/citation/15354201/Death_receptor_4__DR4__efficiently_kills_breast_cancer_cells_irrespective_of_their_sensitivity_to_tumor_necrosis_factor_related_apoptosis_inducing_ligand__TRAIL__ L2 - https://doi.org/10.1038/sj.cgt.7700747 DB - PRIME DP - Unbound Medicine ER -