Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line T47D.
Estrogen receptor (ER) beta counteracts the activity of ERalpha in many systems. In agreement with this, we show in this study that induced expression of ERbeta in the breast cancer cell line T47D reduces 17beta-estradiol-stimulated proliferation when expression of ERbeta mRNA equals that of ERalpha. Induction of ERbeta reduces growth of exponentially proliferating cells with a concomitant decrease in components of the cell cycle associated with proliferation, namely cyclin E, Cdc25A (a key regulator of Cdk2), p45(Skp2) (a key regulator of p27(Kip1) proteolysis), and an increase in the Cdk inhibitor p27(Kip1). We also observed a reduced Cdk2 activity. These findings suggest a possible role for ERbeta in breast cancer and imply that ERbeta-specific ligands may reduce proliferation of ER-positive breast cancer cells through actions on the G(1) phase cell-cycle machinery.
Ström
Anders
A
Department of Biosciences, Karolinska Institutet, Novum, S-14157 Huddinge, Sweden.
Hartman
Johan
J
Foster
James S
JS
Kietz
Silke
S
Wimalasena
Jay
J
Gustafsson
Jan-Ake
JA
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D019938:Cyclin D1 / Q000235:genetics; D017931:DNA Primers; D004958:Estradiol / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047629:Estrogen Receptor beta; D005434:Flow Cytometry; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D020687:cdc25 Phosphatases / Q000235:genetics
D017931:DNA Primers; D020847:Estrogen Receptor Modulators; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D019938:Cyclin D1; D004958:Estradiol; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases