TY - JOUR
T1 - Oestrogens and selective oestrogen receptor (ER) modulators regulate EGF receptor gene expression through human ER α and β subtypes via an Sp1 site
AU - Salvatori, Luisa
AU - Pallante, Pierlorenzo
AU - Ravenna, Linda
AU - Chinzari, Patrizia
AU - Frati, Luigi
AU - Russo, Matteo A.
AU - Petrangeli, Elisa
PY - 2003/7/31
Y1 - 2003/7/31
N2 - Through the analysis of the transient expression of the luciferase reporter gene in HeLa cells, an evaluation has been made of the transcriptional activity of oestrogens and of selective oestrogen receptor (ER) modulators (SERMs), mediated by the α and β isoforms of the ER, on the epidermal growth factor receptor gene promoter. Oestrogen-activated ERβ presents a lower transcriptional activity compared with ERα, probably due to structural differences in the AF-1 regions of the receptors. Also SERMs induce different responses depending on the receptor isoform bound. Indeed, the phyto-oestrogens, genistein and daidzein, act as weak agonists of the oestrogenic activity via ERα, but as full agonists when bound to ERβ. The synthetic SERM 4OH-tamoxifen, on the other hand, displays an opposite behaviour since it exerts a full agonist action through ERα, but acts as a full antagonist via ERβ. As we have previously shown for ERα, an ERβ/Sp1 functional synergism has also been highlighted, by means of gel mobility shift assays. Moreover, our results show that the sensitivity of target tissues to oestrogens and SERMs can be affected by coexpression of ERs, depending on the formation of appropriate levels of homo- and heterodimers, thus providing a useful approach to predict the effects of hormonal treatment.
AB - Through the analysis of the transient expression of the luciferase reporter gene in HeLa cells, an evaluation has been made of the transcriptional activity of oestrogens and of selective oestrogen receptor (ER) modulators (SERMs), mediated by the α and β isoforms of the ER, on the epidermal growth factor receptor gene promoter. Oestrogen-activated ERβ presents a lower transcriptional activity compared with ERα, probably due to structural differences in the AF-1 regions of the receptors. Also SERMs induce different responses depending on the receptor isoform bound. Indeed, the phyto-oestrogens, genistein and daidzein, act as weak agonists of the oestrogenic activity via ERα, but as full agonists when bound to ERβ. The synthetic SERM 4OH-tamoxifen, on the other hand, displays an opposite behaviour since it exerts a full agonist action through ERα, but acts as a full antagonist via ERβ. As we have previously shown for ERα, an ERβ/Sp1 functional synergism has also been highlighted, by means of gel mobility shift assays. Moreover, our results show that the sensitivity of target tissues to oestrogens and SERMs can be affected by coexpression of ERs, depending on the formation of appropriate levels of homo- and heterodimers, thus providing a useful approach to predict the effects of hormonal treatment.
KW - EGF receptor
KW - Gene expression
KW - Oestrogen receptor
KW - Oestrogens
KW - SERMs
KW - Sp1
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U2 - 10.1038/sj.onc.1206784
DO - 10.1038/sj.onc.1206784
M3 - Article
C2 - 12894229
AN - SCOPUS:0041565105
VL - 22
SP - 4875
EP - 4881
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 31
ER -