title: Estrogen induced expression of tissue factor pathway inhibitor-2 in MCF7 cells involves lysine-specific demethylase 1.
abstract: Hormone-sensitive cancers can be influenced by estrogens, a process usually mediated through the estrogen receptor (ER). Tissue factor pathway inhibitor type 2 (TFPI-2) is a Kunitz-type serine protease inhibitor involved in regulating the extracellular matrix. The present study demonstrates that the expression of TFPI-2 can be induced by estrogens. Breast cancer data from GOBO displayed increased levels of TFPI-2 and increased survival in patients with ERα+ tumors. Treatment of MCF7 cells (ERα+) with 17β-estradiol (E2) or 17α-ethinyl estradiol (EE2) increased TFPI-2 mRNA and protein levels. This effect was mitigated with fulvestrant and by knocking down ERα, indicating that estrogen mediated TFPI-2 induction was through ERα. Upon knock down of DNA cytosine-5 methyltransferase 1 (DNMT1) or lysine-specific demethylase 1 (LSD1) in MCF7 cells, reduced effect of E2 on TFPI-2 mRNA levels was observed. Our data thus suggest that estrogen induced TFPI-2 expression in MCF7 cells is mediated by ERα and also by the action of LSD1.
authors.affiliation: Department of Haematology, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Marianne S
authors.initials: MS
authors.lastname: Andresen
authors.affiliation: Department of Haematology, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway; Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway.
authors.forename: Huda Omar
authors.initials: HO
authors.lastname: Ali
authors.affiliation: Department of Haematology, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Christiane Filion
authors.initials: CF
authors.lastname: Myklebust
authors.affiliation: Department of Haematology, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway; Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway.
authors.forename: Per Morten
authors.initials: PM
authors.lastname: Sandset
authors.affiliation: Department of Haematology, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Stavik
authors.affiliation: Dept. of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Iversen
authors.affiliation: Department of Haematology, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway. Electronic address: grethe.skretting@medisin.uio.no.
authors.forename: Grethe
authors.initials: G
authors.lastname: Skretting
mesh_terms: D001374:Azacitidine / Q000494:pharmacology; D018899:CpG Islands / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D056466:Histone Demethylases / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D006023:Glycoproteins; D012333:RNA, Messenger; C021240:tissue-factor-pathway inhibitor 2; D056466:Histone Demethylases; C495195:KDM1A protein, human; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; C000619380:DNMT1 protein, human; D001374:Azacitidine
keywords: Demethylation; ERα; Estrogen; LSD1; MCF7 cells; TFPI-2