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ERα is a negative regulator of PD-L1 gene transcription in breast cancer

Lu Liu1, Yinghui Shen1, Xuguo Zhu1

  • 1Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.

Biochemical and Biophysical Research Communications
|September 23, 2018
PubMed

Insights

Estrogen receptor alpha (ERα) acts as a negative regulator of programmed death-ligand 1 (PD-L1) in breast cancer. Lower ERα levels correlate with higher PD-L1, potentially promoting tumor immune evasion.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Tumor expression of programmed death-ligand 1 (PD-L1) suppresses antitumor immunity by inhibiting T cells via programmed death-1 (PD-1) interaction.
  • PD-L1 is expressed in some ERα-negative breast cancers, but the role of estrogen receptor (ER) signaling in regulating PD-L1 is unclear.

Purpose of the Study:

  • To investigate the relationship between estrogen receptor alpha (ERα) and PD-L1 expression in breast cancer.
  • To determine if ERα signaling influences PD-L1 gene expression.

Main Methods:

  • Analysis of Comprehensive Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) datasets.
  • Experimental manipulation of ERα and E2 (estrogen) levels in breast cancer cell lines (MCF7 and MDA-MB-231).
  • Measurement of PD-L1 mRNA and protein expression.

Main Results:

  • PD-L1 mRNA levels were significantly lower in ERα-positive breast cancer cell lines compared to ERα-negative ones.
  • E2 treatment reduced PD-L1 mRNA in hormone-depleted ERα-positive MCF7 cells.
  • Ectopic ERα expression in ERα-negative MDA-MB-231 cells decreased PD-L1 mRNA and protein levels.
  • TCGA data showed an inverse correlation between ERα and PD-L1 expression in ERα-positive breast cancer.

Conclusions:

  • Estrogen receptor alpha (ERα) functions as a negative regulator of PD-L1 gene transcription in breast cancer cells.
  • Loss of ERα function may enhance breast cancer immune evasion through increased PD-L1 expression.
Keywords:
Breast cancerERαPD-L1

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