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

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