Journal Article

15-Deoxy-Δ<sup>12,14</sup>-prostaglandin J<sub>2</sub> 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 and Young-Joon Surh

in Carcinogenesis

Volume 29, issue 4, pages 688-695
Published in print April 2008 | ISSN: 0143-3334
Published online January 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm299
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

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

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.

Journal Article.  6478 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.