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Title: Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop

Abstract

The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the enzyme telomerase which is responsible for telomeric maintenance and extension. Using RNA interference to knock down hTERT mRNA expression, we provide evidence that hTERT exerts extra-telomeric effects on the cell cycle and on its own regulatory proteins, specifically: p53 and p21. We tested our hypothesis that hTERT regulates its own expression through effects on upstream regulatory genes using transformed human embryonic kidney (HEK 293) cells, p53 and p16 {sup INK4a} null human ovarian cancer SKOV-3 cells, and p53-null MDA-MB-157 human mammary cancer cells. In HEK 293 cells, hTERT knockdown resulted in elevated p53 and p21 transcription and a decrease in cellular proliferation. Similar results were observed in the MDA-MB-157 cell line where p21 was upregulated, correlating with cell growth inhibition. In contrast, we observed a decrease in expression of p21 in SKOV-3 cells with hTERT knockdown and cell growth appeared to be unaffected. These findings suggest that hTERT may be involved in a feedback loop system, thereby playing a role in its own regulation.

Authors:
 [1];  [1]; ;  [1];  [2]
  1. Department of Biology, University of Alabama at Birmingham, AL 35294 (United States)
  2. Department of Biology, University of Alabama at Birmingham, AL 35294 (United States) and Center for Aging, University of Alabama at Birmingham, AL 35294 (United States) and Comprehensive Cancer Center, University of Alabama at Birmingham, AL 25294 (United States). E-mail: trygve@uab.edu
Publication Date:
OSTI Identifier:
20972105
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 2; Other Information: DOI: 10.1016/j.yexcr.2006.10.014; PII: S0014-4827(06)00439-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL CYCLE; CELL PROLIFERATION; ENZYMES; GENES; GROWTH; INHIBITION; KIDNEYS; NEOPLASMS; RNA; TRANSCRIPTION

Citation Formats

Lai, Serene R., Cunningham, Amanda P., Huynh, Vu Q., Andrews, Lucy G., and Tollefsbol, Trygve O. Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2006.10.014.
Lai, Serene R., Cunningham, Amanda P., Huynh, Vu Q., Andrews, Lucy G., & Tollefsbol, Trygve O. Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop. United States. doi:10.1016/j.yexcr.2006.10.014.
Lai, Serene R., Cunningham, Amanda P., Huynh, Vu Q., Andrews, Lucy G., and Tollefsbol, Trygve O. Mon . "Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop". United States. doi:10.1016/j.yexcr.2006.10.014.
@article{osti_20972105,
title = {Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop},
author = {Lai, Serene R. and Cunningham, Amanda P. and Huynh, Vu Q. and Andrews, Lucy G. and Tollefsbol, Trygve O.},
abstractNote = {The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the enzyme telomerase which is responsible for telomeric maintenance and extension. Using RNA interference to knock down hTERT mRNA expression, we provide evidence that hTERT exerts extra-telomeric effects on the cell cycle and on its own regulatory proteins, specifically: p53 and p21. We tested our hypothesis that hTERT regulates its own expression through effects on upstream regulatory genes using transformed human embryonic kidney (HEK 293) cells, p53 and p16 {sup INK4a} null human ovarian cancer SKOV-3 cells, and p53-null MDA-MB-157 human mammary cancer cells. In HEK 293 cells, hTERT knockdown resulted in elevated p53 and p21 transcription and a decrease in cellular proliferation. Similar results were observed in the MDA-MB-157 cell line where p21 was upregulated, correlating with cell growth inhibition. In contrast, we observed a decrease in expression of p21 in SKOV-3 cells with hTERT knockdown and cell growth appeared to be unaffected. These findings suggest that hTERT may be involved in a feedback loop system, thereby playing a role in its own regulation.},
doi = {10.1016/j.yexcr.2006.10.014},
journal = {Experimental Cell Research},
number = 2,
volume = 313,
place = {United States},
year = {Mon Jan 15 00:00:00 EST 2007},
month = {Mon Jan 15 00:00:00 EST 2007}
}