Estrogen induced expression of tissue factor pathway inhibitor-2 in MCF7 cells involves lysine-specific demethylase 1. (5th March 2017)

• Record Type: Journal Article
• Authors: Andresen, Marianne S.; Ali, Huda Omar; Myklebust, Christiane Filion; Sandset, Per Morten; Stavik, Benedicte; Iversen, Nina; Skretting, Grethe
• Is Part Of: Molecular and cellular endocrinology. Volume 443(2017)
• Page Start: 80
• Page End: 88
• Publication Date: 2017-03-05
• Subjects: Estrogen -- TFPI-2 -- MCF7 cells -- Demethylation -- ERα -- LSD1; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2017.01.016
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Highlights: High expression of TFPI-2 is associated with increased survival of patients with ERα+ tumors. Estrogens increase TFPI-2 expression in MCF7 cells. LSD1 knock down inhibits effect of estrogens on TFPI-2 expression.