Thyroid Hormone T3 Induces DNA Damage Response in Breast Cancer Cells

Area of Science:

• Endocrinology
• Molecular Biology
• Genomics

Background:

• Thyroid hormones (THs) are crucial regulators of cellular metabolism, proliferation, and genomic stability.
• Clinical observations link levothyroxine therapy to higher Oncotype DX Recurrence Scores in breast cancer (BC), suggesting TH signaling influences genomic risk.

Purpose of the Study:

• To investigate the impact of triiodothyronine (T3) on DNA damage and repair pathways in breast cancer cells.
• To explore the potential mechanistic link between TH therapy and BC recurrence risk.

Main Methods:

• Exposure of estrogen receptor-positive T47D breast cancer and MCF10A cells to T3.
• RNA sequencing to analyze gene expression changes, focusing on DNA repair.
• Immunofluorescence microscopy to detect DNA damage markers (γH2AX, 53BP1).

Main Results:

• T3 exposure upregulated RAD51 and DNA repair pathways within 24 hours.
• T3 induced transient increases in γH2AX and 53BP1 foci, indicating DNA damage response (DDR) activation.
• These DDR markers returned to baseline after 48 hours, suggesting cellular adaptation; proliferation effects varied with concentration.

Conclusions:

• Acute T3 exposure induces transient genomic stress in breast cancer cells.
• This transient genomic stress provides a potential mechanism for the association between TH therapy and increased BC recurrence risk.