High consumption of
phytoestrogen-rich food correlates with reduced incidence of
breast cancer. However, the effect of
phytoestrogens on growth of pre-existing
breast tumors presents concerns when planning the use of
phytoestrogens as
chemoprevention st rategy.
Genistein, the active
phytoestrogen in soy, displays weak estrogenic activity mediated by
estrogen receptor (ER) with a preferential binding for the ER-beta species. However, no information is at present available on the interaction between
phytoestrogens and the various
isoforms generated by alternative splicing. In two human
breast cancer cell lines, T47D and BT20, which express variable levels of ER-beta, the effect of
genistein and
quercetin was evaluated singly and in comparison with 17beta-estradiol, on
mRNA expression of
estrogen receptor-beta (ER-beta)
isoforms evaluated by a triple primer RT-PCR assay. In T47D cells
estradiol caused a 6-fold up-regulation of total ER-beta, and modified the relative expression pattern of the various
isoforms, up-regulating the beta2 and down-regulating the beta5
isoform.
Genistein up-regulated ER-beta2 and ER-beta1 in T47D cells, and
after treatment the ER-beta2
isoform became prevalent, while in BT20 cells it almost doubled the percent contribution of ER-beta1 and ER-beta2 to total ER-beta.
Quercetin did not alter the total levels nor the percent distribution of ER-beta
isoforms in either cell line.
Genistein, through the modulation of ER-beta
isoform RNA expression inhibited
estrogen-promoted cell growth, without interfering on
estrogen-regulated transcription. ER-beta and its ER-beta
mRNA isoforms may be involved in a self-limiting mechanism of estrogenic stimulation promoted either by the natural
hormone or by weaker
estrogen agonists like
genistein.