Abstract

Primary wild type, COX-1-/- and COX-2-/- keraticytes were transfected with a retrovirus containing v-ras and the transfected keratinocytes grafted on to the back of athymic nude mice. Tumor growth from transfected COX-2 -/- keratinocytes was markedly reduced compared to transfected WT, while COX-1-/- keratinocytes showed only slightly reduced tumor growth. Tumor incidence was also reduced in mice grafted with the COX-2 -/- keratinocytes. The number of blood vessels per square cm of tumor did not differ with keratinocyte genotype. We did observe lower proliferation rates and higher levels of terminal differentiation in the COX-2 -/- keratinocytes compared to WT keratinocytes as indicated by lowed BRDU incorporation and increased keratin 1 expression. The lower levels of cell replication and increased terminal differentiation were likely causes of COX-2-/- keratinocytes giving rise to fewer and smaller tumors in this grafting model.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021231-08
Application #
7593871
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2007
Total Cost
$183,041
Indirect Cost

  Institution

Name
National Institute of Environmental Health Sciences
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