Selective Estrogen Receptor Modulators' (SERMs) Influence on TET3 Expression in Breast Cancer Cell Lines with...

Area of Science:

• Epigenetics
• Molecular Oncology
• Pharmacology

Background:

• Estrogen signaling is crucial in breast cancer, influencing gene expression and epigenetic modifications.
• Tamoxifen, a selective estrogen receptor modulator (SERM), has dual agonist/antagonist effects via estrogen nuclear receptor (ESR) or G-protein-coupled estrogen receptor (GPER).
• Epigenetic alterations, like DNA methylation, are key in cancer development and progression.

Purpose of the Study:

• To investigate the impact of tamoxifen derivatives on DNA methylation patterns in breast cancer.
• To explore the role of TET3 (ten-eleven translocation 3) in mediating these epigenetic changes.
• To assess the influence of estrogen receptor status on tamoxifen's epigenetic effects.

Main Methods:

• Utilized three breast cancer cell lines (MCF-7, MDA-MB-231, SkBr3) with varying ESR and GPER expression.
• Treated cells with 4-hydroxytamoxifen (4-HT) and endoxifen (Endox).
• Quantified 5-methylcytosine (5-mC) levels and TET3 mRNA expression using 2D HPLC-MS/MS.

Main Results:

• MCF-7 cells (ESR+/GPER+) showed the highest 5-mC levels and lowest TET3 expression.
• 4-HT treatment significantly altered TET3 expression across cell lines, with the greatest increase in MCF-7.
• Tamoxifen derivatives influenced DNA methylation, with TET3 modulation dependent on estrogen receptor presence.

Conclusions:

• Tamoxifen derivatives can modify DNA methylation patterns in breast cancer cells.
• TET3 expression is a key mediator of these tamoxifen-induced epigenetic changes.
• Targeting epigenetic modifications, influenced by tamoxifen and estrogen receptors, offers potential for personalized breast cancer therapy.