Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 48
Estrogen receptor-mediated transcriptional regulation may involve different cross-talk
interaction between estrogen receptor and xenobiotic nuclear receptors depending on
the estrogen target cell types
Gyesik Min
Department of Microbiological Engineering, Jinju National University, Jinju,
Gyeongsangnam-Do, 660-758 South Korea E-mail: g-min@jinju.ac.kr
The purpose of this study was to examine the effects of xenobiotic nuclear receptors, CAR,
SXR, and PPARgamma on the transcriptional activity of estrogen receptor in human breast
cancer cell lines and compare with those in human hepatoma cell line. Three different breast
cancer cell lines, MCF-7 with ER expression, MDA-MB-231 without ER expression, and
MCF-7K3 with estrogen-independent growth were cultured and effects of CAR, SXR, and
PPARgamma on the ER-mediated transcriptional activation of synthetic (4ERE)-tk-luciferase
reporter gene were analyzed. Consistent with the previous report, CAR significantly inhibited
ER-mediated transactivation and SXR repressed modestly whereas the PPARgamma did not
repress the ER-mediated transactivation in Hep G2 cells. However, in breast cancer cells
neither of the xenobiotic receptors repressed the ER-mediated transactivation. Instead, they
tend to increase the transactivation depending on the cell type and xenobiotic nuclear
receptors. In MCF-7, SXR but not CAR or PPARgamma slightly increased ER-mediated
transactivation whereas in MDA-MB-231, CAR and PPARgamma but not SXR tend to
increase the transactivation of the reporter gene. In addition, in MCF-7K3 only high dose of
CAR slightly increased estrogen dependent ER transactivation. These results indicate that the
effects of cross-talk in ER-mediated transactivation between estrogen and the xenobiotic
nuclear receptors, CAR, SXR, PPARgamma, are different in breast cancer cells from
hepatoma cells. Different responses to each xenobiotic receptor from the three breast cancer
cell lines may suggest diverse signal transduction pathways for the receptors, CAR, SXR,
PPARgamma, present in different breast cancer cell lines. In conclusion, the transcriptional
regulation by estrogen in ER-mediated transactivation can involve different cross-talk
interaction between estrogen receptor and xenobiotic nuclear receptors depending on the
estrogen target cell types.
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