C/EBPβ at the core of the TGFβ cytostatic response and its evasion in metastatic breast cancer cells Journal Article
| Authors: | Gomis, R. R.; Alarcón, C.; Nadal, C.; Van Poznak, C.; Massague, J. |
| Article Title: | C/EBPβ at the core of the TGFβ cytostatic response and its evasion in metastatic breast cancer cells |
| Abstract: | Breast cancers may evade the growth-inhibitory action of TGFβ by accumulating defects of unknown nature that selectively eliminate cytostatic gene responses. We found the transcription factor C/EBPβ to be essential for TGFβ 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/EBPβ inhibitory isoform LIP. We suggest that C/EBPβ plays a key role in the coordination of TGFβ cytostatic gene responses, and its malfunction may trigger evasion of these responses in breast cancer. © 2006 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; human cell; promoter region; genetics; nonhuman; pathophysiology; molecular genetics; cell proliferation; animal cell; mouse; animal; metabolism; animals; mice; animal tissue; cell cycle; disease association; metastasis; breast cancer; smad protein; transforming growth factor beta; animal experiment; animal model; drug effect; pathology; tumor cells, cultured; breast neoplasms; dna; regulatory mechanism; molecular sequence data; cell culture; nucleotide sequence; myc protein; breast tumor; gene repression; neoplasm metastasis; transactivation; epithelium cell; base sequence; binding protein; cellcycle; proto-oncogene proteins c-myc; oncogene myc; cytostasis; transcription factor foxo; ccaat enhancer binding protein beta; ccaat-enhancer-binding protein-beta; cyclin-dependent kinase inhibitor p15; cyclin dependent kinase inhibitor 2b; promoter regions (genetics); trans-activation (genetics); coordination |
| Journal Title: | Cancer Cell |
| Volume: | 10 |
| Issue: | 3 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2006-09-01 |
| Start Page: | 203 |
| End Page: | 214 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2006.07.019 |
| PUBMED: | 16959612 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 82" - "Export Date: 4 June 2012" - "CODEN: CCAEC" - "Source: Scopus" |
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5Gomis -
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Van Poznak -
4
Nadal -
388Massague -
8
Alarcon
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