Interaction between estrogen receptor alpha, ionizing radiation and (anti-) estrogens in breast cancer cells.
OBJECTIVE
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. The aim of this study is to evaluate the potential interference between radiotherapy and estrogen receptor responsiveness. Materials and methods. The effect of ionizing radiation was assessed on the estrogen receptor alpha status, growth (proliferation and apoptosis) and sensitivity of MCF-7 breast cancer cells 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 in ERalpha of these cells. On the other hand, E2 impedes the growth inhibitory effects (essentially on proliferation) of ionizing radiation in MCF-7 cells, which potentially decreases radiosensitivity of these cells. This effect was totally blocked by SERM and anti-estrogenic treatments. 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.
Toillon
R A
RA
Laboratoire Jean-Claude Heuson de Cancérologie Mammaire Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium.
Magné
N
N
Laïos
I
I
Lacroix
M
M
Duvillier
H
H
Lagneaux
L
L
Devriendt
D
D
Van Houtte
P
P
Leclercq
G
G
D000704:Analysis of Variance; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000528:radiation effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002453:Cell Cycle / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol