[Cell-biology] The effects of gamma-irradiation on MCF-7 breast cancer cell line, and their modulation by estrogens.

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Tue Mar 6 04:43:13 EST 2007

“Estrogens decrease γ-ray–induced senescence and maintain cell cycle
progression in breast cancer cells independently of p53”

by Robert-Alain Toillon (1), Nicolas Magné (2), Ioanna Laïos (1),
Pierre Castadot (2), Eric Kinnaert (2), Paul Van Houtte (2), Christine
Desmedt (3), Guy Leclercq (1), Marc Lacroix (1)(4).
(1) Jean-Claude Heuson Breast Cancer Laboratory, Free University of
Brussels, Brussels, Belgium; (2) Radiotherapy Unit and (3) Microarray
Unit, Jules Bordet Institute, Brussels, Belgium; (4) InTextoResearch,
Baelen, Wallonia, Belgium

published in International Journal of Radiation Oncology Biology
Physics (2007) 67, 1187-1200


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-β-estradiol (E2, a natural estrogen) on the MCF-7
breast cancer cell line.

Results: Our results showed that E2 sustained the growth of IR-cells.
Specifically, estrogens prevented cell cycle blockade induced by γ-
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 E2 on the
p53/p21waf1/cip1/Rb pathways. We found that E2 did not affect p53
activation but it decreased cyclin E binding to p21waf1/cip1 and
sustained downstream Rb hyperphosphorylation by functional
inactivation of p21waf1/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
E2 after irradiation-induced damage. They also offer clinicians a
rational basis for the sequential administration of ionizing radiation
and endocrine therapies.

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