TRAMP carcinogenesis is associated with a loss of COX expression and resistance to the tumor suppressive effects of omega-3 fatty acids.
Creators:Smolinski, Justin B.
Advisor:Clinton, Steven K.
Colby, Jennifer K.
Fischer, Susan M.
Klein, Russell D.
MetadataShow full item record
Series/Report no.:Interdisciplinary Ph.D. Program in Nutrition - OSUN. Graduate student poster competition, 2007
It is hypothesized that diets rich in omega-3 fatty acids, such as found in many fish, may be preventive against prostate cancer. It is hypothesized that these fatty acids exert chemopreventive effects through a suppression of PGE2 and enhancement of PGE3 synthesis, reducing proinflammatory signals and/or enhancing antiproliferative/proapoptotic signaling. We have chosen to investigate the effects of a high fish oil diet on prostate cancer chemoprevention with the TRAMP model of prostate cancer. This transgenic mouse develops invasive adenocarcinoma of the prostate as a result of androgen-driven, prostate-specific expression of the SV-40 T/t antigen. Male mice (4 week old) were placed on diets containing 40% of calories from fish oil (HFO) or corn oil (HCO) for 26 weeks. Time to 2cm diameter palpable tumor was recorded. Tissues were collected and concentrations of tissue fatty acids and prostaglandins were obtained. Prostate tumorigenesis was not altered by lipid source. However, prostatic lipid profiles mimicked dietary changes. In addition, prostatic PGE2 was reduced by the HFO diet in wild-type mice, but no changes in TRAMP mice. PGE3 was increased by HFO diet in wild-type and transgenic mice. We observed that COX expression was significantly lost during progression of TRAMP carcinogenesis. These studies suggest that fatty acid and lipid metabolism are disrupted in the TRAMP model in a manner that produces resistance to dietary intervention. In conclusion, the HFO diet did not prevent prostatic tumorigenesis in the TRAMP model but did affect levels of PGE2 and PGE3 and substrates for their metabolism.
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