Abstract

Epidemiological studies in humans have shown a marked decrease in colon and other cancers that correlates with the use of nonsteroidal antiinflammatory drugs (NSAIDs). We have demonstrated that COX-1 and COX-2 deficiencies reduce skin tumorigenesis and believe this reduction is due to altered differentiation. By IHC and western analysis of keratins we have demonstrated differences in terminal differentiation between the wild type and COX null mice. COX2 appears to affect the promotion phase of skin carcinogenesis via its effects on cell replication and differentiation, while COX1, in addition to its effects on differentiation, may influence initiation through modulation of apoptosis in DMBA initiated stem cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021231-01
Application #
6413343
Study Section
(ECM)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
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; 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
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
Gray, Thomas; Nettesheim, Paul; Loftin, Charles et al. (2004) Interleukin-1beta-induced mucin production in human airway epithelium is mediated by cyclooxygenase-2, prostaglandin E2 receptors, and cyclic AMP-protein kinase A signaling. Mol Pharmacol 66:337-46
Schneider, Andre; Guan, YouFei; Zhang, Yahua et al. (2004) Generation of a conditional allele of the mouse prostaglandin EP4 receptor. Genesis 40:7-14
Goulet, Jennifer L; Pace, Amy J; Key, Mikelle L et al. (2004) E-prostanoid-3 receptors mediate the proinflammatory actions of prostaglandin E2 in acute cutaneous inflammation. J Immunol 173:1321-6
Takeda, Haruna; Sonoshita, Masahiro; Oshima, Hiroko et al. (2003) Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal polyposis. Cancer Res 63:4872-7
Tiano, Howard F; Loftin, Charles D; Akunda, Jackie et al. (2002) Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res 62:3395-401