Estrogen induced expression of tissue factor pathway inhibitor-2 in MCF7 cells involves lysine-specific demethylase 1

Area of Science:

• Endocrinology
• Molecular Biology
• Cancer Research

Background:

• Hormone-sensitive cancers are influenced by estrogens, often via the estrogen receptor (ER).
• Tissue Factor Pathway Inhibitor type 2 (TFPI-2) regulates the extracellular matrix and is a Kunitz-type serine protease inhibitor.
• TFPI-2 expression is investigated in relation to estrogen signaling in cancer.

Purpose of the Study:

• To investigate the effect of estrogens on Tissue Factor Pathway Inhibitor type 2 (TFPI-2) expression.
• To determine the role of estrogen receptor alpha (ERα) in estrogen-induced TFPI-2 expression.
• To explore the involvement of epigenetic modifiers in this process.

Main Methods:

• Analysis of breast cancer data (GOBO) for TFPI-2 levels and patient survival.
• Treatment of MCF7 cells (ERα+) with estrogens (17β-estradiol, 17α-ethinyl estradiol) and anti-estrogen (fulvestrant).
• Gene knockdown of ERα, DNA cytosine-5 methyltransferase 1 (DNMT1), and lysine-specific demethylase 1 (LSD1).
• Measurement of TFPI-2 mRNA and protein levels.

Main Results:

• Increased TFPI-2 levels and improved survival were observed in ERα+ tumors.
• Estrogens significantly increased TFPI-2 mRNA and protein in MCF7 cells.
• The estrogen-induced TFPI-2 expression was dependent on ERα, as shown by fulvestrant treatment and ERα knockdown.
• Knockdown of DNMT1 or LSD1 reduced the effect of estrogen on TFPI-2 mRNA levels.

Conclusions:

• Estrogen induces TFPI-2 expression in ERα-positive breast cancer cells.
• Estrogen receptor alpha (ERα) is the primary mediator of this induction.
• Epigenetic factors, specifically LSD1, also play a role in estrogen-mediated TFPI-2 expression.