C/EBPbeta at the core of the TGFbeta cytostatic response and its evasion in metastatic breast cancer cells

Cancer Cell. 2006 Sep;10(3):203-14. doi: 10.1016/j.ccr.2006.07.019.


Breast cancers may evade the growth-inhibitory action of TGFbeta by accumulating defects of unknown nature that selectively eliminate cytostatic gene responses. We found the transcription factor C/EBPbeta to be essential for TGFbeta induction of the cell cycle inhibitor p15INK4b by a FoxO-Smad complex and repression of c-MYC by an E2F4/5-Smad complex in human epithelial cells. These cytostatic responses are selectively missing in metastatic breast cancer cells from half of the patients that we tested. The basis for this loss was traced to an excess of the C/EBPbeta inhibitory isoform LIP. We suggest that C/EBPbeta plays a key role in the coordination of TGFbeta cytostatic gene responses, and its malfunction may trigger evasion of these responses in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p15 / metabolism
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neoplasm Metastasis
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured


  • CCAAT-Enhancer-Binding Protein-beta
  • Cyclin-Dependent Kinase Inhibitor p15
  • Proto-Oncogene Proteins c-myc
  • Transforming Growth Factor beta