Interaction between estrogen receptor alpha, ionizing radiation and
(anti)-estrogens in breast cancer cells.
by Robert-Alain Toillon, Nicolas Magné, Ioanna Laïos, Marc Lacroix,
Hughes Duvillier, Laurence Lagneaux, Paul VanHoutte, Guy Leclercq
Institut Jules Bordet Institute, Bruxelles (Brussels), Belgique
(Belgium)
in Breast Cancer research and Treatment (2005) 93, 207-215
http://www.geocities.com/m.lacroix/bcrt6.htm
Purpose: Estrogen receptor alpha (ERalpha) plays a major role in breast
cancer development. It acts as ligand-inducible transcription factor
which determines growth, survival and differentiation of breast cancer
cells (BCC). The aim of this study was to evaluate the potential
interference between radiotherapy and estrogen receptor responsiveness.
Materials and methods: The effect of ionizing radiation was assessed on
the ERalpha status, growth
(proliferation and apoptosis) and sensitivity of MCF-7 BCC to
estrogenic (17beta-estradiol (E2)), selective estrogen receptor
modulator (SERM) and anti-estrogenic compounds.
Results: We have observed a ligand-independent decrease in ERalpha
expression after radiation, resulting from a specific reduction in mRNA
level and protein synthesis. This ERalpha disappearance occurred 72 h
post-irradiation at 8 Gy and decreased the transcriptional activity of
ERalpha in MCF-7 BCC. On the other hand, E2 impeded the growth
inhibitory effects (essentially on proliferation) of ionizing radiation
in MCF-7 BCC, indicating a potential decrease in radiosensitivity of
these cells. This effect was totally blocked by SERM and
anti-estrogenic treatments (4-hydroxy-tamoxifen and ICI 182,780).
Moreover, this growth effect of concurrent anti-estrogenic drugs and
ionizing radiation appeared to be strongly synergistic.
Conclusions: This study may increase general comprehension of ERalpha
modulation by radiotherapy and improve adjuvant therapeutic approaches
based on co-administration of radiation and endocrine therapy.
