Estrogen receptor-beta 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 ERalpha positive cells but its association with ERalpha negative status in-vivo raising the possibility that S100A7 might be regulated by ERbeta in breast cancer. Using doxycycline-inducible ERbeta and ERalpha expressing MCF-7 cells the hypothesis that psoriasin/S100A7 is ERbeta regulated was investigated To explore the relationship between psoriasin/S100A7 and ERbeta expression in-vivo, we also assessed a cohort of 233 ERalpha negative breast tumors using tissue microarrays and immunohistochemistry. Psoriasin/S100A7 was increased by 17beta-estradiol (E2) following ERbeta induction, in several clones of ERbeta over-expressing but not in the original MCF-7 cells, nor clones over-expressing ERalpha. The effect of E2 on psoriasin/S100A7 was inhibited by 4-hydroxytamoxifen and ICI 182780 but not with a selective ERalpha antagonist. An ERbeta selective-agonist but not an ERalpha selective-agonist, induced psoriasin/S100A7. This induction still occurred after stable down-regulation of ERalpha using siRNA in ERbeta inducible cells. E2 increased psoriasin/S100A7 mRNA but cycloheximide treatment inhibited this effect. A relationship between ERbeta 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 ERbeta in-vitro and associated with ERbeta in-vivo. These data support the hypothesis that psoriasin/S100A7 is specifically regulated by ERbeta activity and could be useful to guide future therapies targeting ERbeta in certain phenotypic subsets of breast cancers in-vivo.
Skliris
George P
GP
Department of Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, Canada.
Lewis
Anthony
A
Emberley
Ethan
E
Peng
Baocheng
B
Weebadda
Wineeta K
WK
Kemp
Angela
A
Davie
James R
JR
Shiu
Robert P C
RP
Watson
Peter H
PH
Murphy
Leigh C
LC
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D017931:DNA Primers; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000473:pathology; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D047629:Estrogen Receptor beta; D012334:RNA, Neoplasm; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human