Abstract

The major goal of the study was the elucidation of the role of prostaglandin E2 (PGE2) receptors (EP) in mouse skin tumorigenesis. Epidemiological studies in humans have confirmed an important role of PGs, including PGE2, in a variety of cancers including skin cancer. PGE2 produced via the cyclooxygenases (COX-1/COX-2) act on four different cell surface receptors (EP 1, -2, -3, -4), which belong to the family of GPCRs. We found that the EP2 and EP4 receptors were over-expressed in papillomas, but only the EP2, and not EP4, receptor was involved in tumor formation. EP2 was involved in the activation of several signaling cascades commonly associated with a variety of cancers. In summary, we show that Ras expression and activation and EGFR activation are regulated by EP2 and that EP2 contributes to papilloma development by activating proliferation and pro-survival pathways.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES102145-01
Application #
7330707
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2006
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Chun, Kyung-Soo; Lao, Huei-Chen; Trempus, Carol S et al. (2009) The prostaglandin receptor EP2 activates multiple signaling pathways and beta-arrestin1 complex formation during mouse skin papilloma development. Carcinogenesis 30:1620-7
Chun, Kyung-Soo; Langenbach, Robert (2007) A proposed COX-2 and PGE(2) receptor interaction in UV-exposed mouse skin. Mol Carcinog 46:699-704
Akunda, Jacqueline K; Chun, Kyung-Soo; Sessoms, Alisha R et al. (2007) Cyclooxygenase-2 deficiency increases epidermal apoptosis and impairs recovery following acute UVB exposure. Mol Carcinog 46:354-62
Fischer, Susan M; Pavone, Amy; Mikulec, Carol et al. (2007) Cyclooxygenase-2 expression is critical for chronic UV-induced murine skin carcinogenesis. Mol Carcinog 46:363-71
Chun, Kyung-Soo; Akunda, Jacqueline K; Langenbach, Robert (2007) Cyclooxygenase-2 inhibits UVB-induced apoptosis in mouse skin by activating the prostaglandin E2 receptors, EP2 and EP4. Cancer Res 67:2015-21
Rao, Jagadeesh S; Langenbach, Robert; Bosetti, Francesca (2005) Down-regulation of brain nuclear factor-kappa B pathway in the cyclooxygenase-2 knockout mouse. Brain Res Mol Brain Res 139:217-24