A triad of telomerase, androgen receptor and early growth response 1 in prostate cancer cells

Telomerase activation is one of the key mechanisms that allow cells to bypass replicative senescence. Telomerase activity is primarily regulated at the level of transcription of its catalytic unit- hTERT. Prostate cancer (PCa), akin to other cancers, is characterized by high telomerase activity. Exi...

Full description

Saved in:
Bibliographic Details
Published in:Cancer biology & therapy 2016-04, Vol.17 (4), p.439-448
Main Authors: Jacob, Sheeba, Nayak, Sumeet, Kakar, Ruchi, Chaudhari, Uddhav K., Joshi, Dolly, Vundinti, Babu R., Fernandes, Gwendolyn, Barai, Ram S., Kholkute, Sanjeeva D., Sachdeva, Geetanjali
Format: Article
Language:English
Subjects:
Androgen receptor
Antibodies, Monoclonal - metabolism
Cell Line, Tumor
Cell Proliferation
EGR-1
hTERT
Humans
Male
prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Receptors, Androgen - metabolism
Research Paper
Signal Transduction
telomerase
Telomerase - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Telomerase activation is one of the key mechanisms that allow cells to bypass replicative senescence. Telomerase activity is primarily regulated at the level of transcription of its catalytic unit- hTERT. Prostate cancer (PCa), akin to other cancers, is characterized by high telomerase activity. Existing data suggest that hTERT expression and telomerase activity are positively regulated by androgenic stimuli in androgen-dependent prostate cancer (ADPC) cells. A part of the present study reaffirmed this by demonstrating a decline in the hTERT expression and telomerase activity on "loss of AR" in ADPC cells. The study further addressed 2 unresolved queries, i) whether AR-mediated signaling is of any relevance to hTERT expression in castration-resistant prostate cancer (CRPC) and ii) whether this signaling involves EGR1. Our data suggest that AR-mediated signaling negatively regulates hTERT expression in CRPC cells. Incidental support for the possibility of EGR1 being a regulator of hTERT expression in PCa was provided by i) immunolocalization of hTERT and EGR1 proteins in the same cell type (secretory epithelium) of PCa and BPH tissues; ii) significantly (p< 0.001) higher levels of both these proteins in CRPC (PC3 and DU145), compared with ADPC (LNCaP) cells. A direct evidence for the role of EGR1 in hTERT expression was evident by a significant (p
ISSN:1538-4047
1555-8576
DOI:10.1080/15384047.2016.1156255