15-Deoxy-Δ12,14-prostaglandin J2 induces COX-2 expression through Akt-driven AP-1 activation in human breast cancer cells: A potential role of ROS

Eun Hee Kim, Hye Kyung Na, Do Hee Kim, Sin Aye Park, Ha Na Kim, Na Young Song, Young Joon Surh

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63 Citations (Scopus)


Recent studies suggest that inflammation is causally linked to carcinogenesis. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the biosynthesis of prostaglandins, is inappropriately expressed in various cancers and hence recognized as one of the hallmarks of chronic inflammation-associated malignancies. However, the mechanistic role of COX-2 as a link between inflammation and cancer remains undefined. Here, we report that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of the final products of COX-mediated arachidonic acid metabolism, upregulates the expression of COX-2 in the human breast cancer MCF-7 cell line. 15d-PGJ2 -induced COX-2 expression was mediated by activation of Akt and subsequently activator protein-1 (AP-1). Furthermore, 15d-PGJ2 formed reactive oxygen species, which led to increased phosphorylation of Akt, DNA binding of AP-1 and expression of COX-2. In contrast to 15d-PGJ2, 9,10-dihydro-15d-PGJ2 did not elicit any of effects induced by 15d-PGJ2 in this study, suggesting that an electrophilic carbon center present in 15d-PGJ2 is critical for COX-2 expression as well activation of upstream signal transduction induced by this cyclopentenone prostaglandin. Taken together, these observations suggest that 15d-PGJ2 produced by COX-2 overexpression may function as a positive regulator of COX-2 in human breast cancer MCF-7 cells.

Original languageEnglish
Pages (from-to)688-695
Number of pages8
Issue number4
Publication statusPublished - 2008 Apr

Bibliographical note

Funding Information:
Korea Science and Engineering Foundation through the National Research Laboratory Program (M10400000366-06J0000-36610); Innovative Drug Research Center through the Ministry of Science and Technology.

All Science Journal Classification (ASJC) codes

  • Cancer Research


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