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Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines

Marilyn Carrier1, Mathilde Joint2, Régis Lutzing1

  • 1Department of Functional Genomics and Cancer, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), INSERM, U964, CNRS, UMR7104, Université de Strasbourg, 1 rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, Strasbourg, France.

Plos One
|July 1, 2016
PubMed

Insights

Retinoic acid (RA) exhibits anti-cancer effects, but resistance varies in breast cancer cells. This study reveals that RA resistance may stem from altered protein phosphorylation and gene expression patterns.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Retinoic acid (RA), the active metabolite of vitamin A, regulates crucial cellular processes like proliferation and differentiation.
  • RA demonstrates anti-cancer properties, yet some breast cancer cells exhibit resistance to its effects.
  • The precise molecular mechanisms underlying RA resistance, particularly concerning signaling and transcriptional pathways, remain incompletely understood.

Purpose of the Study:

  • To compare the phosphoproteome and RA-regulated genes in RA-responsive (MCF7) versus RA-resistant (BT474) human breast cancer cell lines.
  • To elucidate the signaling and transcriptional alterations associated with RA resistance.
  • To investigate the role of protein phosphorylation in mediating RA effects and resistance.

Main Methods:

  • Utilized high-resolution nano-LC-LTQ-Orbitrap mass spectrometry for large-scale phosphoproteomic analysis.
  • Performed phosphopeptide enrichment to identify differentially phosphorylated proteins.
  • Conducted genome-wide analysis to identify RA-regulated genes in both cell lines.

Main Results:

  • Identified differential phosphorylation of signaling and transcription-related proteins in response to RA between MCF7 and BT474 cells.
  • Observed that the retinoic acid receptor alpha (RARα) was phosphorylated in RA-responsive MCF7 cells but not in RA-resistant BT474 cells upon RA addition.
  • Demonstrated distinct sets of RA-regulated genes in the two cell lines, suggesting altered transcriptional responses.

Conclusions:

  • RA resistance in breast cancer cells correlates with deregulation of the phosphoproteome.
  • Altered protein phosphorylation patterns significantly impact RA-mediated gene expression and cellular responses.
  • These findings provide insights into the molecular basis of RA resistance and suggest potential therapeutic targets.

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