Estrogen receptor-β regulates psoriasin (S100A7) in human breast cancer

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Abstract
We have previously observed a paradoxical relationship of the psoriasin/S100A7 gene with estrogen response in-vitro in ERα positive cells but its association with ERα negative status in-vivo raising the possibility that S100A7 might be regulated by ERβ in breast cancer. Using doxycycline-inducible ERβ and ERα expressing MCF-7 cells the hypothesis that psoriasin/S100A7 is ERβ regulated was investigated To explore the relationship between psoriasin/S100A7 and ERβ expression in-vivo, we also assessed a cohort of 233 ERα negative breast tumors using tissue microarrays and immunohistochemistry. Psoriasin/S100A7 was increased by 17β-estradiol (E2) following ERβ induction, in several clones of ERβ over-expressing but not in the original MCF-7 cells, nor clones over-expressing ERα. The effect of E2 on psoriasin/S100A7 was inhibited by 4-hydroxytamoxifen and ICI 182780 but not with a selective ERα antagonist. An ERβ selective-agonist but not an ERα selective-agonist, induced psoriasin/S100A7. This induction still occurred after stable down-regulation of ERα using siRNA in ERβ inducible cells. E2 increased psoriasin/S100A7 mRNA but cycloheximide treatment inhibited this effect. A relationship between ERβ and psoriasin/S100A7 was observed in the p53 immunohistochemically negative subset of invasive breast tumors in-vivo (r = 0.225, p = 0.046, n = 79). In conclusion we demonstrate that E2 induction of psoriasin/S100A7 can be specifically regulated through ERβ in-vitro and associated with ERβ in-vivo. These data support the hypothesis that psoriasin/S100A7 is specifically regulated by ERβ activity and could be useful to guide future therapies targeting ERβ in certain phenotypic subsets of breast cancers in-vivo.