Genomic profiling of C/EBPβ2 transformed mammary epithelial cells: a role for nuclear interleukin-1β

Cancer Biol Ther. 2010 Sep 1;10(5):509-19. doi: 10.4161/cbt.10.5.12725. Epub 2010 Sep 21.

Abstract

C/EBPβ is essential for mammary gland growth and development and has been associated with poor prognosis in breast cancer. Overexpression of C/EBPβ2 in MCF10A cells results in a variety of cancer phenotypes including EMT and ErbB independence. IL1β is dramatically upregulated in MCF10A-C/EBPβ2 cells but there is little, if any, processing to the mature 17 kD form. Although proIL1b has previously been considered to be biologically inactive, we demonstrate proIL1b is not only localized to the nucleus, but is also tightly associated with the chromatin. We show that proIL1β is bound at specific locations in the genome and is positioned in such a way to play a role in the cancer phenotypes observed in MCF10A-C/EBPβ2 cells. Moreover, nuclear IL1β is detected in some human breast tumor samples. This study demonstrates the presence of nuclear proIL1β in transformed mammary epithelial cells providing the first evidence that IL1β may be a dual function cytokine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Transformation, Neoplastic
  • Chromatin / genetics
  • Chromatin / metabolism
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Mammary Glands, Human / cytology
  • Mammary Glands, Human / growth & development
  • Mammary Glands, Human / metabolism*
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Receptors, Interleukin-1 Type II / genetics
  • Signal Transduction

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • CEBPB protein, human
  • Chromatin
  • Interleukin-1beta
  • Protein Precursors
  • Receptors, Interleukin-1 Type II