Abstract Number: LPB0071
Meeting: ISTH 2021 Congress
Background: Coagulation factor (F) V is an influential regulator of blood coagulation and has been shown to be increased in breast tumors. Cancer contributes to activation of the coagulation system leading to an imbalance in the hemostatic system. Most breast tumors express estrogen receptor (ER) where estrogen signaling plays an important role.
Aims: To explore the molecular association between estrogens and FV in ERα positive breast cancer cells.
Methods: MCF-7 cells were treated with 17-β-estradiol (E2) or 17-β-ethinylestradiol (EE2) alone or in combination with the ER antagonist fulvestrant. ERα was also transiently knocked down prior to stimulation with estrogen. F5 mRNA and FV protein levels were measured using qRT-PCR and Western blotting. Potential estrogen responsive elements (ERE) within the F5 promoter were identified by bioinformatic analysis. The F5 5’-flanking region containing wild type or mutated EREs were cloned into a luciferase reporter gene vector and transfected into MCF-7 cells prior to estrogen stimulation. Kaplan-Meyer survival analysis of F5 mRNA in ER positive tumors from breast cancer patients in the Kaplan-Meier plotter database were performed.
Results: The expression of F5 mRNA and FV protein levels were significantly increased in cells after stimulation with the natural E2 or synthetic EE2, in a dose- and time-dependent manner. Treatment with fulvestrant or knockdown of ERα counteracted this upregulation. Significantly increased luciferase activity was observed in E2 treated cells transfected with the F5 wild type promoter construct containing the potential ERE binding sites. This effect was abolished when all three ERE sites were destroyed. High F5 mRNA levels in ER positive tumors were associated with increased relapse-free survival in a clinical breast cancer material.
Conclusions: We demonstrate that F5 is an estrogen responsive gene in breast cancer cells expressing ERα and that high F5 levels in ER positive breast cancer was associated with relapse-free survival.
To cite this abstract in AMA style:Seierstad Andresen M, Sletten M, Sandset PM, Iversen N, Stavik* B, Tinholt* M. Coagulation Factor 5 (F5) Is an Estrogen-responsive Gene in Breast Cancer Cells [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/coagulation-factor-5-f5-is-an-estrogen-responsive-gene-in-breast-cancer-cells/. Accessed December 8, 2021.
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