A major goals of this work are the elucidation of the roles of COX-1 and COX-2 in the tumorigenesis process. Epidemiological studies in humans have shown a marked decrease in several types of 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 intestinal tumorigenesis and believe this reduction is due to premature terminal differentiation of initiated cells. This premature onset of terminal differentiation would continually remove initiated cell from the replicative population and decrease tumor growth and numbers. To extend these studies we have determined whether COX isoform selective inhibitors, like COX deficiency, would alter keratinocyte differentiation and also reduce mouse skin tumorigenesis. Furthermore, Because the prostaglandins (PG)produced via the cyclooxygenases cause their effects by interacting with a family of G protein coupled receptors we have used Real Time PCR to investigated changes in PG receptor levels as skin tumor development occurs. The data indicate that COX selective inhibitors, like COX deficiency, also reduce skin tumorigenesis, and that PG receptor levels do change during skin tumor development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021231-05
Application #
7006566
Study Section
(LECM)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2004
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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