Androgen regulates apoptosis induced by TNFR family ligands via multiple signaling pathways in LNCaP

Oskar W Rokhlin; Agshin F Taghiyev; Natalya V Guseva; Rebecca A Glover; Peter M Chumakov; Julia E Kravchenko; Michael B Cohen

doi:10.1038/sj.onc.1208833

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Androgen regulates apoptosis induced by TNFR family ligands via multiple signaling pathways in LNCaP

Journal article

Peer reviewed

Androgen regulates apoptosis induced by TNFR family ligands via multiple signaling pathways in LNCaP

Oskar W Rokhlin, Agshin F Taghiyev, Natalya V Guseva, Rebecca A Glover, Peter M Chumakov, Julia E Kravchenko and Michael B Cohen

Oncogene, Vol.24(45), pp.6773-6784

10/13/2005

DOI: 10.1038/sj.onc.1208833

PMCID: PMC1361275

PMID: 16007156

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https://www.ncbi.nlm.nih.gov/pmc/articles/1361275View

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Abstract

It has been suggested in many studies that combined treatment with chemotherapeutic agents and apoptosis-inducing ligands belonging to TNFR family is a more effective strategy for cancer treatment. However, the role of androgen regulation of TNFR family-induced apoptosis in prostate cancer is poorly understood. In this study, we investigated the dose-dependent effects of androgen on TNF-α and TRAIL-mediated apoptosis in LNCaP. To investigate the interaction between the androgen receptor (AR) and the caspase-2 gene, chromatin immunoprecipitation analysis was used, and we are the first to identify that AR interacts in vivo with an androgen-responsive elements in intron 8 of caspase-2 gene. We have found that DHT inhibited apoptosis in dose-dependent manner. There is a direct, androgen-dependent correlation between the levels of activated Akt and caspase activation after treatment with TNF-α and TRAIL. We have also found that there are at least two different regulatory mechanisms of p53 expression by androgen: at the gene and protein levels. At the same time, the level of AR was found to be higher in LNCaP-si-p53 compared to LNCaP-mock cells. These data indicate that there is a mutual regulation of expression between p53 and AR. Our study suggests that androgen-dependent outcome of apoptotic treatment can occur, at least in part, via the caspase-2, Akt and p53-mediated pathways.

Cell Physiology

Signal Transduction

Ageing, cell death

Biological and medical sciences

Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes

Fundamental and applied biological sciences. Psychology

Molecular and cellular biology

Details

Title: Subtitle: Androgen regulates apoptosis induced by TNFR family ligands via multiple signaling pathways in LNCaP
Creators: Oskar W Rokhlin - University of Iowa
Agshin F Taghiyev - University of Iowa
Natalya V Guseva - University of Iowa
Rebecca A Glover - University of Iowa
Peter M Chumakov - Cleveland Clinic
Julia E Kravchenko - Cleveland Clinic
Michael B Cohen - University of Iowa
Resource Type: Journal article
Publication Details: Oncogene, Vol.24(45), pp.6773-6784
DOI: 10.1038/sj.onc.1208833
PMID: 16007156
PMCID: PMC1361275
NLM abbreviation: Oncogene
ISSN: 0950-9232
eISSN: 1476-5594
Publisher: Nature Publishing
Language: English
Date published: 10/13/2005
Academic Unit: Pathology; Biology
Record Identifier: 9984647058302771

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