Overexpression of BAD potentiates sensitivity to tumor necrosis factor-related apoptosis-inducing ligand treatment in the prostatic carcinoma cell line LNCaP

Agshin F Taghiyev; Natalya V Guseva; Hisashi Harada; C Michael Knudson; Oskar W Rokhlin; Michael B Cohen

Back

Overexpression of BAD potentiates sensitivity to tumor necrosis factor-related apoptosis-inducing ligand treatment in the prostatic carcinoma cell line LNCaP

Journal article

Peer reviewed

Overexpression of BAD potentiates sensitivity to tumor necrosis factor-related apoptosis-inducing ligand treatment in the prostatic carcinoma cell line LNCaP

Agshin F Taghiyev, Natalya V Guseva, Hisashi Harada, C Michael Knudson, Oskar W Rokhlin and Michael B Cohen

Molecular cancer research, Vol.1(7), pp.500-507

05/2003

PMID: 12754297

View Online

Abstract

Here we show that LNCaP, which is resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, becomes sensitive to TRAIL after overexpression of full-length, wild-type BAD (BAD WT). TRAIL induces caspase-dependent cleavage of BAD WT that results in generation of a M(r) 15,000 protein. LNCaP stably expressing truncated BAD (tBAD) and cells expressing mutated BAD at the caspase cleavage site were less sensitive to TRAIL treatment when compared to LNCaP expressing BAD WT. Cytochrome c and Smac/DIABLO release from mitochondria into cytosol was found after TRAIL treatment only in cells overexpressing BAD WT. Furthermore, differences in phosphorylation of serine residues for BAD WT and tBAD were identified. BAD WT was phosphorylated at positions S136 and S155, whereas tBAD was phosphorylated at positions S112, S136, and S155. LNCaP stably expressing BAD mutated at serine 112 to alanine was less sensitive to TRAIL treatment when compared to LNCaP expressing BAD WT. Lastly, recombinant BAD cleaved by caspase-3 is a more potent inducer of cytochrome c and Smac/DIABLO release than BAD WT. In summary, BAD-mediated sensitivity of LNCaP to TRAIL depends on the phosphorylation status of BAD WT and tBAD.

Prostatic Neoplasms - pathology

Phosphorylation

Apoptosis - drug effects

Cell Survival

Humans

Membrane Glycoproteins - pharmacology

Gene Expression Regulation, Neoplastic

Male

Mitochondria - metabolism

Carrier Proteins - genetics

Tumor Necrosis Factor-alpha - pharmacology

Animals

Apoptosis Regulatory Proteins

Caspases - metabolism

TNF-Related Apoptosis-Inducing Ligand

Caspase 3

Cytosol - metabolism

Mice

Tumor Cells, Cultured

Proto-Oncogene Proteins c-bcl-2 - genetics

bcl-Associated Death Protein

Details

Title: Subtitle: Overexpression of BAD potentiates sensitivity to tumor necrosis factor-related apoptosis-inducing ligand treatment in the prostatic carcinoma cell line LNCaP
Creators: Agshin F Taghiyev - Department of Pathology, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242-1087, USA
Natalya V Guseva
Hisashi Harada
C Michael Knudson
Oskar W Rokhlin
Michael B Cohen
Resource Type: Journal article
Publication Details: Molecular cancer research, Vol.1(7), pp.500-507
Publisher: United States
PMID: 12754297
ISSN: 1541-7786
eISSN: 1557-3125
Grant note: CA 87617 / NCI NIH HHS
Language: English
Date published: 05/2003
Academic Unit: Stead Family Department of Pediatrics; Pathology; Radiation Oncology
Record Identifier: 9984047723402771

Metrics

29 Record Views

20 Times Cited - Web of Science