Raloxifene induces nucleolar translocation of the estrogen receptor.
Raloxifene (RLX), a selective estrogen receptor modulator (SERM), binds to the estrogen receptor alpha (ERalpha) and acts as an agonist in some tissues, and as an antagonist in others. To clarify the molecular mechanism underlying the tissue specificity of SERMs, we examined the intracellular localization of ERalpha using a green fluorescent protein (GFP)-tagged protein in culture cells from various tissues. Although ERalpha formed intranuclear foci in the presence of estradiol (E(2)), RLX translocated ERalpha into the nucleoli in breast cancer cell lines. This phenomenon was not observed in cells from other tissues. Immunofluorescence staining revealed that endogenous ERalpha was also translocated into the nucleoli in the presence of RLX. Mutation analyses demonstrate that helix 12 of ERalpha is essential to the nucleolar translocation of ERalpha. These results suggest that translocation of ERalpha into the nucleoli is RLX-specific and is a key event for RLX-induced growth repression of mammary gland cells.
Gushima
Mika
M
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Kawate
Hisaya
H
Ohnaka
Keizo
K
Nomura
Masatoshi
M
Takayanagi
Ryoichi
R
D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism*; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D017433:Protein Structure, Secondary / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology
D047628:Estrogen Receptor alpha; D020845:Selective Estrogen Receptor Modulators; D049452:Green Fluorescent Proteins; D020849:Raloxifene Hydrochloride