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

Breast cancers may evade the growth-inhibitory action of TGFO by accumulating defects of unknown nature that selectively eliminate cytostatic gene responses. We found the transcription factor C/EBPO to be essential for TGFO induction of the cell cycle inhibitor p151NK4b 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/EBPO inhibitory isoform LIP. We suggest that C/EBPO plays a key role in the coordination of TGFO cytostatic gene responses, and its malfunction may trigger evasion of these responses in breast cancer.