title: The histone demethylase LSD1 is required for estrogen-dependent S100A7 gene expression in human breast cancer cells.
abstract: S100A7, a member of S100 calcium binding protein family, is highly associated with breast cancer. However, the molecular mechanism of S100A7 regulation remains unclear. Here we show that long-term treatment with estradiol stimulated S100A7 expression in MCF7 breast cancer cells at both the transcriptional and translational levels. Both treatment with a histone demethylase LSD1 inhibitor and shRNA-based knockdown of LSD1 expression significantly decreased 17β-estradiol (E2)-induced S100A7 expression. These reduced E2-mediated S100A7 expression are rescued by the overexpressed wild-type LSD1 but not by its catalytically inactive mutant. Our data showed in vivo association of LSD1 with S100A7 promoters, confirming the potential role of LSD1 in regulating S100A7 expression. S100A7 knockdown increased both normal cell growth and estrogen-induced cell proliferation, suggesting a negative influence by S100A7 on the growth of cancer cells. Together, our data suggest that estrogen-induced S100A7 expression mediated by the histone demethylase LSD1 may downregulate breast cancer cell proliferation, implying a potential tumor suppressor-like function for S100A7.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Seung Eun
authors.initials: SE
authors.lastname: Yu
authors.forename: Yeun Kyu
authors.initials: YK
authors.lastname: Jang
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics*
chemical_list: D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D004958:Estradiol; D056466:Histone Demethylases; C495195:KDM1A protein, human