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The p75{sup NTR} tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells

Abstract

The p75 neurotrophin receptor (p75{sup NTR}) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75{sup NTR} retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted ({delta}DD) dominant-negative antagonist of p75{sup NTR} showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75{sup NTR}-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75{sup NTR} expressing cells occurred via the intrinsic mitochondrial pathway leading to a sequential caspase-9 and -7 cascade. Since the death domain deleted dominant-negative antagonist of p75{sup NTR} rescued intrinsic caspase associated apoptosis in PC-3 cells, this shows p75{sup NTR} was integral to ligand independent induction of apoptosis. Moreover, the ability of ligand to ameliorate the p75{sup NTR}-dependent intrinsic apoptotic cascade indicates that NGF functioned as a survival factor for p75{sup NTR} expressing  More>>
Authors:
Khwaja, Fatima; [1]  Tabassum, Arshia; [2]  Allen, Jeff; [3]  Djakiew, Daniel [4] 
  1. Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057-1436 (United States)
  2. Toronto Western Hospital, Toronto, ON, M5T258 (Canada)
  3. National Center for Complementary and Alternative Medicine, N.I.H., Bethesda, MD 20892 (United States)
  4. Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057-1436 (United States) and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057-1436 (United States)
Publication Date:
Mar 24, 2006
Product Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 341; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2006.01.073; PII: S0006-291X(06)00159-8; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL CYCLE; DEATH; INHIBITION; LIGANDS; NEOPLASMS; PROSTATE; RECEPTORS; TUMOR CELLS
OSTI ID:
20798856
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0006-291X; BBRCA9; TRN: US06R0271100945
Submitting Site:
INIS
Size:
page(s) 1184-1192
Announcement Date:
Dec 20, 2006

Citation Formats

Khwaja, Fatima, Tabassum, Arshia, Allen, Jeff, and Djakiew, Daniel. The p75{sup NTR} tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.01.073.
Khwaja, Fatima, Tabassum, Arshia, Allen, Jeff, & Djakiew, Daniel. The p75{sup NTR} tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells. United States. doi:10.1016/j.bbrc.2006.01.073.
Khwaja, Fatima, Tabassum, Arshia, Allen, Jeff, and Djakiew, Daniel. 2006. "The p75{sup NTR} tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells." United States. doi:10.1016/j.bbrc.2006.01.073. https://www.osti.gov/servlets/purl/10.1016/j.bbrc.2006.01.073.
@misc{etde_20798856,
title = {The p75{sup NTR} tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells}
author = {Khwaja, Fatima, Tabassum, Arshia, Allen, Jeff, and Djakiew, Daniel}
abstractNote = {The p75 neurotrophin receptor (p75{sup NTR}) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75{sup NTR} retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted ({delta}DD) dominant-negative antagonist of p75{sup NTR} showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75{sup NTR}-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75{sup NTR} expressing cells occurred via the intrinsic mitochondrial pathway leading to a sequential caspase-9 and -7 cascade. Since the death domain deleted dominant-negative antagonist of p75{sup NTR} rescued intrinsic caspase associated apoptosis in PC-3 cells, this shows p75{sup NTR} was integral to ligand independent induction of apoptosis. Moreover, the ability of ligand to ameliorate the p75{sup NTR}-dependent intrinsic apoptotic cascade indicates that NGF functioned as a survival factor for p75{sup NTR} expressing prostate cancer cells.}
doi = {10.1016/j.bbrc.2006.01.073}
journal = {Biochemical and Biophysical Research Communications}
issue = {4}
volume = {341}
place = {United States}
year = {2006}
month = {Mar}
}