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Down-regulation and growth inhibitory role of C/EBPalpha in breast cancer

Sigal Gery1, Sakae Tanosaki, Shikha Bose

  • 1Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine, USA. gerys@cshs.org

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 4, 2005
PubMed
Abstract

Insights

Reduced expression of CCAAT/enhancer binding protein alpha (C/EBPalpha) is linked to breast cancer development. Lower C/EBPalpha levels correlate with aggressive tumor types and inhibit cancer cell growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • CCAAT/enhancer binding proteins (C/EBP) are crucial transcription factors regulating cell proliferation and differentiation.
  • The role of C/EBPalpha in breast cancer pathogenesis remains largely unexplored.

Purpose of the Study:

  • To investigate the involvement of C/EBPalpha in breast cancer.
  • To analyze C/EBPalpha expression patterns in breast tumors and cell lines.

Main Methods:

  • Quantification of C/EBPalpha mRNA using quantitative real-time reverse transcription-PCR.
  • Assessment of C/EBPalpha protein levels via immunohistochemical analysis.
  • Functional studies involving stable transfection of inducible C/EBPalpha expression vectors in breast cancer cell lines.

Main Results:

  • 83% of breast cancers showed low C/EBPalpha mRNA expression; 30% had reduced or undetectable protein.
  • C/EBPalpha expression inversely correlated with estrogen and progesterone receptor status.
  • Induced C/EBPalpha expression inhibited cell growth, caused G0-G1 cell cycle arrest, and reduced anchorage-independent growth.
  • C/EBPalpha modulated expression of key genes including c-myc, p21, PPARgamma, and maspin.

Conclusions:

  • Reduced C/EBPalpha expression is implicated in breast cancer development and progression.
  • C/EBPalpha may function as a tumor suppressor in breast tissue.

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