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Title: Estrogens decrease {gamma}-ray-induced senescence and maintain cell cycle progression in breast cancer cells independently of p53

Abstract

Purpose: Sequential administration of radiotherapy and endocrine therapy is considered to be a standard adjuvant treatment of breast cancer. Recent clinical reports suggest that radiotherapy could be more efficient in association with endocrine therapy. The aim of this study was to evaluate the estrogen effects on irradiated breast cancer cells (IR-cells). Methods and Materials: Using functional genomic analysis, we examined the effects of 17-{beta}-estradiol (E{sub 2}, a natural estrogen) on MCF-7 breast cancer cells. Results: Our results showed that E{sub 2} sustained the growth of IR-cells. Specifically, estrogens prevented cell cycle blockade induced by {gamma}-rays, and no modification of apoptotic rate was detected. In IR-cells we observed the induction of genes involved in premature senescence and cell cycle progression and investigated the effects of E{sub 2} on the p53/p21{sup waf1/cip1}/Rb pathways. We found that E{sub 2} did not affect p53 activation but it decreased cyclin E binding to p21{sup waf1/cip1} and sustained downstream Rb hyperphosphorylation by functional inactivation of p21{sup waf1/cip1}. We suggest that Rb inactivation could decrease senescence and allow cell cycle progression in IR-cells. Conclusion: These results may help to elucidate the molecular mechanism underlying the maintenance of breast cancer cell growth by E{sub 2} after irradiation-induced damage.more » They also offer clinicians a rational basis for the sequential administration of ionizing radiation and endocrine therapies.« less

Authors:
 [1];  [2];  [3];  [2];  [2];  [2];  [4];  [3];  [3]
  1. Laboratoire Jean-Claude Heuson de Cancerologie Mammaire, Universite Libre de Bruxelles, Brussels (Belgium). E-mail: robert.toillon@univ-lille1.fr
  2. Radiotherapy Unit, Institut Jules Bordet, Brussels (Belgium)
  3. Laboratoire Jean-Claude Heuson de Cancerologie Mammaire, Universite Libre de Bruxelles, Brussels (Belgium)
  4. Microarray Unit, Institut Jules Bordet, Brussels (Belgium)
Publication Date:
OSTI Identifier:
20944779
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2006.11.040; PII: S0360-3016(06)03596-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; CELL CYCLE; DNA DAMAGES; ESTRADIOL; GAMMA RADIATION; GENES; GROWTH; INACTIVATION; IRRADIATION; MAMMARY GLANDS; NEOPLASMS; RADIOTHERAPY

Citation Formats

Toillon, Robert-Alain, Magne, Nicolas, Laios, Ioanna, Castadot, Pierre, Kinnaert, Eric, Van Houtte, Paul, Desmedt, Christine B.Sc., Leclercq, Guy, and Lacroix, Marc. Estrogens decrease {gamma}-ray-induced senescence and maintain cell cycle progression in breast cancer cells independently of p53. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.11.040.
Toillon, Robert-Alain, Magne, Nicolas, Laios, Ioanna, Castadot, Pierre, Kinnaert, Eric, Van Houtte, Paul, Desmedt, Christine B.Sc., Leclercq, Guy, & Lacroix, Marc. Estrogens decrease {gamma}-ray-induced senescence and maintain cell cycle progression in breast cancer cells independently of p53. United States. doi:10.1016/j.ijrobp.2006.11.040.
Toillon, Robert-Alain, Magne, Nicolas, Laios, Ioanna, Castadot, Pierre, Kinnaert, Eric, Van Houtte, Paul, Desmedt, Christine B.Sc., Leclercq, Guy, and Lacroix, Marc. Thu . "Estrogens decrease {gamma}-ray-induced senescence and maintain cell cycle progression in breast cancer cells independently of p53". United States. doi:10.1016/j.ijrobp.2006.11.040.
@article{osti_20944779,
title = {Estrogens decrease {gamma}-ray-induced senescence and maintain cell cycle progression in breast cancer cells independently of p53},
author = {Toillon, Robert-Alain and Magne, Nicolas and Laios, Ioanna and Castadot, Pierre and Kinnaert, Eric and Van Houtte, Paul and Desmedt, Christine B.Sc. and Leclercq, Guy and Lacroix, Marc},
abstractNote = {Purpose: Sequential administration of radiotherapy and endocrine therapy is considered to be a standard adjuvant treatment of breast cancer. Recent clinical reports suggest that radiotherapy could be more efficient in association with endocrine therapy. The aim of this study was to evaluate the estrogen effects on irradiated breast cancer cells (IR-cells). Methods and Materials: Using functional genomic analysis, we examined the effects of 17-{beta}-estradiol (E{sub 2}, a natural estrogen) on MCF-7 breast cancer cells. Results: Our results showed that E{sub 2} sustained the growth of IR-cells. Specifically, estrogens prevented cell cycle blockade induced by {gamma}-rays, and no modification of apoptotic rate was detected. In IR-cells we observed the induction of genes involved in premature senescence and cell cycle progression and investigated the effects of E{sub 2} on the p53/p21{sup waf1/cip1}/Rb pathways. We found that E{sub 2} did not affect p53 activation but it decreased cyclin E binding to p21{sup waf1/cip1} and sustained downstream Rb hyperphosphorylation by functional inactivation of p21{sup waf1/cip1}. We suggest that Rb inactivation could decrease senescence and allow cell cycle progression in IR-cells. Conclusion: These results may help to elucidate the molecular mechanism underlying the maintenance of breast cancer cell growth by E{sub 2} after irradiation-induced damage. They also offer clinicians a rational basis for the sequential administration of ionizing radiation and endocrine therapies.},
doi = {10.1016/j.ijrobp.2006.11.040},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 67,
place = {United States},
year = {Thu Mar 15 00:00:00 EDT 2007},
month = {Thu Mar 15 00:00:00 EDT 2007}
}