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 trezatments (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.
