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Regulation of HER-2 oncogene expression by cyclooxygenase-2 and prostaglandin E2

Oncogene volume 23, pages 1631–1635 (2004)Cite this article

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.

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Acknowledgements

V Benoit is Research Assistant, A Chariot and M-P Merville are Research Associates at the National Fund for Scientific Research (Belgium). This research was supported by the ‘Leon Fredericq Foundation’, the ‘Centre Anticancéreux près l'Ulg’ (Liège, Belgium) and by grants from Télévie and the National Fund for Scientific Research (Belgium).

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Authors and Affiliations

  1. Laboratory of Medical Chemistry and Human Genetics, Center for Molecular and Cellular Therapy, University of Liège, Belgium

    Valérie Benoit, Alain Chariot, Marie-Paule Merville & Vincent Bours

  2. Laboratory of Rheumatology, Center for Molecular and Cellular Therapy, University of Liège, Belgium

    Biserka Relic

  3. Natural and Synthetic Drugs Research Center, University of Liège, Belgium

    Xavier de Leval

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  1. Valérie Benoit
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  2. Biserka Relic
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  3. Xavier de Leval
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Correspondence to Vincent Bours.

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Benoit, V., Relic, B., Leval, X. et al. Regulation of HER-2 oncogene expression by cyclooxygenase-2 and prostaglandin E2. Oncogene 23, 1631–1635 (2004). https://doi.org/10.1038/sj.onc.1207295

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