Recent studies demonstrated that
constitutive androstane receptor (CAR) inhibits ER-mediated transactivation of both endogenous and
synthetic estrogen responsive promotor in Hep G2. Whereas
steroid and xenobiotic receptor (SXR) but not
peroxisome proliferator-activated receptor-gamma (
PPAR-gamma) was also reported to repress
estrogen receptor (ER) transactivation of the synthetic 4ERE in Hep G2, the effects of these
xenobiotic nuclear receptors (XNRs) on the endogenous
estrogen responsive promotor remain to be determined. Effects of CAR, SXR, and
PPAR-gamma on ER transactivation were also examined in three different kinds of
breast cancer cell lines. However, except in MCF-7, studies were limited either in single dose response (MDA-MB-231) or with CAR only (MCF-7-K3). And there is presently no report on the effects of CAR, SXR, and
PPAR-gamma on ER-mediated transactivation in ovarian-derived CHO-S cells. Accordingly, this article further examined the effects of the endogenous
vitellogenin B1
estrogen responsive promotor on the SXR- and
PPAR-gamma-modulated ER transactivation in Hep G2, and either dose-dependent or single dose effects of SXR,
PPAR-gamma, and CAR in two different
breast cancer cell lines and the ovarian-derived cell line respectively, on the ER-mediated transactivation of the synthetic (4ERE)-tk-luciferase reporter. Consistent with the previous report, CAR significantly repressed ER-mediated transactivation of the endogenous
vitellogenin B1 promotor in Hep G2 cells. However, contrary to the effects on the synthetic promotor,
PPAR-gamma potentiated whereas SXR did not have any effects on the ER transactivation of the
vitellogenin promotor in Hep G2. In the
breast cancer cell line of MDA-MB-231 in which endogenous ER is known not to be expressed, CAR modestly stimulated ER transactivation of the synthetic 4ERE in a low dose whereas both SXR and
PPAR-gamma did not have any effects in all doses examined (20-500 ng). And in both CHO-S and
estrogen-independent
breast cancer cell line, MCF-7-K3, none of the three
xenobiotic receptors significantly influenced the ER-mediated 4ERE transactivation in all doses examined. XNRs modulate ER-mediated transactivation depending on the
estrogen response elements (EREs) and
estrogen target cell types.