TRAIL-DISC formation is androgen-dependent in the human prostatic carcinoma cell line LNCaP

Oskar W Rokhlin; Agshin F Taghiyev; Nataliya V Guseva; Rebecca A Glover; Sergei I Syrbu; Michael B Cohen

doi:10.4161/cbt.311

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TRAIL-DISC formation is androgen-dependent in the human prostatic carcinoma cell line LNCaP

Journal article

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Peer reviewed

TRAIL-DISC formation is androgen-dependent in the human prostatic carcinoma cell line LNCaP

Oskar W Rokhlin, Agshin F Taghiyev, Nataliya V Guseva, Rebecca A Glover, Sergei I Syrbu and Michael B Cohen

Cancer biology & therapy, Vol.1(6), pp.631-637

11/2002

DOI: 10.4161/cbt.311

PMID: 12642685

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Abstract

We and others have previously described that the androgen-responsive human prostatic carcinoma cell line LNCaP is resistant to TRAIL and that TRAIL-mediated apoptosis in LNCaP is PI3K/Akt-dependent. In this study, we found that LNCaP remained resistant to treatment with TRAIL after androgen deprivation even in the presence of the PI3K/Akt pathway inhibitor wortmannin. This resistance was determined by failure to form the TRAIL-DISC and by decreased TRAIL-R1 and TRAIL-R2 levels after androgen deprivation; the capacity of TRAIL to induce DISC formation was completely restored in the presence of DHT. TRAIL and wortmannin together accelerated processing of caspase-8 on the DISC and apparently the release of caspase-8 from the DISC into the cytoplasm. Surprisingly, we found that wortmannin decreased the total amount of TRAIL-R1, but not TRAIL-R2, in the cells as well as the amount of TRAIL-R1 precipitated by TRAIL. Our data suggest that TRAIL-DISC formation and sensitivity to TRAIL treatment are androgen-dependent in LNCaP.

Neoplasms, Hormone-Dependent - metabolism

Prostatic Neoplasms - metabolism

Caspase 9

Caspase 8

Apoptosis - drug effects

Humans

Membrane Glycoproteins - biosynthesis

Protein-Serine-Threonine Kinases

Drug Resistance, Neoplasm

Male

DNA Primers - chemistry

Phosphatidylinositol 3-Kinases - antagonists & inhibitors

Receptors, TNF-Related Apoptosis-Inducing Ligand

Death Domain Receptor Signaling Adaptor Proteins

Caspases - metabolism

TNF-Related Apoptosis-Inducing Ligand

Transfection

Genes, Dominant

Polymerase Chain Reaction

Tumor Cells, Cultured

Receptors, Tumor Necrosis Factor - genetics

Proto-Oncogene Proteins - metabolism

Receptors, Tumor Necrosis Factor - metabolism

Prostatic Neoplasms - pathology

Enzyme Inhibitors - pharmacology

Fas-Associated Death Domain Protein

Blotting, Western

Precipitin Tests

Proto-Oncogene Proteins c-akt

Adaptor Proteins, Signal Transducing

Apoptosis Regulatory Proteins

Carrier Proteins - metabolism

Androstadienes - pharmacology

Signal Transduction - drug effects

Wortmannin

Receptors, Tumor Necrosis Factor - biosynthesis

Androgens - metabolism

Tumor Necrosis Factor-alpha - biosynthesis

Details

Title: Subtitle: TRAIL-DISC formation is androgen-dependent in the human prostatic carcinoma cell line LNCaP
Creators: Oskar W Rokhlin - Department of Pathology, The University of Iowa, Iowa City, Iowa 52242, USA
Agshin F Taghiyev
Nataliya V Guseva
Rebecca A Glover
Sergei I Syrbu
Michael B Cohen
Resource Type: Journal article
Publication Details: Cancer biology & therapy, Vol.1(6), pp.631-637
DOI: 10.4161/cbt.311
PMID: 12642685
NLM abbreviation: Cancer Biol Ther
ISSN: 1538-4047
eISSN: 1555-8576
Publisher: United States
Language: English
Date published: 11/2002
Academic Unit: Stead Family Department of Pediatrics; Pathology; Biology
Record Identifier: 9984047603102771

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