| Abstract | The oncoprotein HER-2/neu is a prosurvival factor and its overexpression has been correlated with adverse prognosis in breast cancers. High levels of the cyclooxygenase-2 (COX-2), a proinflammatory and antiapoptotic enzyme, were detected in HER-2-positive tumors and this observation was linked to an HER-2-mediated induction of COX-2 gene transcription. Here, we report that COX-2 expression, and synthesis of its major enzymatic product, PGE2, leads in turn to an enhanced HER-2 expression. Moreover, COX-2 enzymatic inhibition dramatically reduced HER-2 protein levels, efficiently increased the cancer cells sensitility to chemotherapeutic treatment and acted in synergy with HER-2 inhibitor, trastuzumab. Therefore, we propose an original model where HER-2 and COX-2 transcriptionally regulate each other in a positive loop. |
| Authors | Valérie Benoit, Biserka Relic, Xavier de Leval Xd, Alain Chariot, Marie-Paule Merville, Vincent Bours
(Affiliation: Laboratory of Medical Chemistry and Human Genetics, Center for Molecular and Cellular Therapy, University of Liège, Belgium.)
|
| Journal | Oncogene
(Oncogene)
Vol. 23
Issue 8
Pg. 1631-5
(Feb 26 2004)
ISSN: 0950-9232 England |
| PMID | 14985703
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Isoenzymes
- Membrane Proteins
- RNA, Messenger
- Dinoprostone
- Cyclooxygenase 2
- PTGS2 protein, human
- Prostaglandin-Endoperoxide Synthases
- Receptor, erbB-2
|
| Topics |
- Breast Neoplasms
(metabolism, pathology)
- Cell Line, Tumor
- Cyclooxygenase 2
- Dinoprostone
(biosynthesis)
- Female
- Gene Expression Regulation, Neoplastic
- Genes, erbB-2
- Humans
- Isoenzymes
(metabolism)
- Membrane Proteins
- Models, Genetic
- Prostaglandin-Endoperoxide Synthases
(metabolism)
- RNA, Messenger
(analysis)
- Receptor, erbB-2
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
|
