Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-delta signaling in epithelial ovarian cancer.

Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-delta signaling in epithelial ovarian cancer. Research Abstract Details 

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Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-delta signaling in epithelial ovarian cancer. Abstract Text:

Takiko Daikoku,Susanne Tranguch,Anindita Chakrabarty,Dingzhi Wang,Dineo Khabele,Sandra Orsulic,Jason D Morrow,Raymond N Dubois,Sudhansu K Dey,

The underlying causes of epithelial ovarian cancer (EOC) are unclear, and treatment options for patients with advanced disease are limited. There is evidence that the use of nonsteroidal anti-inflammatory drugs is associated with decreased risk of developing EOC. Nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase (COX)-1 and COX-2, which catalyze prostaglandin biosynthesis. We previously showed that mouse and human EOCs have increased levels of COX-1, but not COX-2, and a COX-1-selective inhibitor, SC-560, attenuates prostaglandin production and tumor growth. However, the downstream targets of COX-1 signaling in EOC are not yet known. To address this question, we evaluated peroxisome proliferator-activated receptor delta (PPARdelta) expression and function in EOC. We found that EOC cells express high levels of PPARdelta, and neutralizing PPARdelta function reduces tumor growth in vivo. More interestingly, aspirin, a nonsteroidal anti-inflammatory drug that preferentially inhibits COX-1, compromises PPARdelta function and cell growth by inhibiting extracellular signal-regulated kinases 1/2, members of the mitogen-activated protein kinase family. Our study, for the first time, shows that whereas PPARdelta can be a target of COX-1, extracellular signal-regulated kinase is a potential target of PPARdelta. The ability of aspirin to inhibit EOC growth in vivo is an exciting finding because of its low cost, lack of cardiovascular side effects, and availability.

Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-delta signaling in epithelial ovarian cancer. Publishing Authors By Initials

T Daikoku,S Tranguch,A Chakrabarty,D Wang,D Khabele,S Orsulic,JD Morrow,RN Dubois,SK Dey,

For similar xenograft model antitumor assays research abstracts see: xenograft model antitumor assays research

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Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-delta signaling in epithelial ovarian cancer. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer research

VOLUME: 67

Page Numbers: 5285-92

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Jun

YEAR: 2007

Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-delta signaling in epithelial ovarian cancer. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-delta signaling in epithelial ovarian cancer. Keywords Mesh Terms:

KEYWORDS: Xenograft Model Antitumor Assays

MESH TERMS: drug effects

Chemical & Substance for Abstract: Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-delta signaling in epithelial ovarian cancer. Information

Substance Name: Mitogen-Activated Protein Kinase 3

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-delta signaling in epithelial ovarian cancer.

AFFILIATION: Department of Pediatrics, Division of Reproductive and Development Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2678, USA.

Country: United States

AGENCY: United States NCI

GRANT: U54CA091405-06

ACRONYM: CA

MEDLINETA: Cancer Res

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