DcR2 (TRAIL-R4) siRNA and adenovirus delivery of TRAIL (Ad5hTRAIL) break down in vitro tumorigenic potential of prostate carcinoma cells

A D Sanlioglu; B Karacay; I T Koksal; T S Griffith; S Sanlioglu

doi:10.1038/sj.cgt.7701087

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DcR2 (TRAIL-R4) siRNA and adenovirus delivery of TRAIL (Ad5hTRAIL) break down in vitro tumorigenic potential of prostate carcinoma cells

Journal article

Peer reviewed

DcR2 (TRAIL-R4) siRNA and adenovirus delivery of TRAIL (Ad5hTRAIL) break down in vitro tumorigenic potential of prostate carcinoma cells

A D Sanlioglu, B Karacay, I T Koksal, T S Griffith and S Sanlioglu

Cancer gene therapy, Vol.14(12), pp.976-984

12/2007

DOI: 10.1038/sj.cgt.7701087

PMID: 17853923

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Abstract

High levels of decoy receptor 2 (DcR2; TRAIL-R4) expression are correlated with TRAIL resistance in prostate cancer cells. In addition, upregulation of TRAIL death receptor (DR4 and DR5) expression, either by ionizing radiation or chemotherapy, can sensitize cancer cells to TRAIL. Considering more than half of human cancers are TRAIL resistant, modulation of surface TRAIL receptor expression appears to be an attractive treatment modality to counteract TRAIL resistance. In this study, three siRNA duplexes targeting DcR2 receptor were tested. Ad5hTRAIL infections were performed to overexpress human full-length TRAIL to induce cell death, and the in vitro tumorigenic potential of prostate cancer cells was assessed using colony-forming assays on soft agar. The DU145 and LNCaP prostate cancer cell lines, which express high levels of DcR2, were resistant to Ad5hTRAIL-induced death. Downregulation of surface DcR2 expression by siRNA sensitized these prostate cancer cell lines to Ad5hTRAIL. In addition, DcR2 siRNA-mediated knockdown of DcR2, followed by Ad5hTRAIL infection, dramatically reduced the in vitro tumorigenic potential of prostate cancer cells. Collectively, our results suggest the potential for combining receptor-specific siRNA with TRAIL in the treatment of certain cancers.

Genetic Therapy

Prostatic Neoplasms - metabolism

RNA, Small Interfering - genetics

Adenoviridae

Tumor Necrosis Factor Decoy Receptors - genetics

Humans

Cercopithecus aethiops

Male

Neoplasm Proteins - antagonists & inhibitors

Receptors, TNF-Related Apoptosis-Inducing Ligand - biosynthesis

Prostatic Neoplasms - therapy

Tumor Necrosis Factor Decoy Receptors - biosynthesis

Cell Death - genetics

RNA, Small Interfering - biosynthesis

Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics

Neoplasm Proteins - genetics

Gene Expression Regulation, Neoplastic - genetics

Receptors, Tumor Necrosis Factor - genetics

Prostatic Neoplasms - pathology

Transduction, Genetic

Neoplasm Proteins - biosynthesis

Up-Regulation - genetics

Down-Regulation - genetics

Animals

Tumor Necrosis Factor Decoy Receptors - antagonists & inhibitors

Cell Line, Tumor

Receptors, Tumor Necrosis Factor - biosynthesis

COS Cells

Details

Title: Subtitle: DcR2 (TRAIL-R4) siRNA and adenovirus delivery of TRAIL (Ad5hTRAIL) break down in vitro tumorigenic potential of prostate carcinoma cells
Creators: A D Sanlioglu - Human Gene Therapy Unit, Akdeniz University, Faculty of Medicine, Antalya, Turkey
B Karacay
I T Koksal
T S Griffith
S Sanlioglu
Resource Type: Journal article
Publication Details: Cancer gene therapy, Vol.14(12), pp.976-984
DOI: 10.1038/sj.cgt.7701087
PMID: 17853923
NLM abbreviation: Cancer Gene Ther
ISSN: 0929-1903
eISSN: 1476-5500
Publisher: England
Language: English
Date published: 12/2007
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984065828702771

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