Carcinogenesis, Vol 19, 985-989, Copyright © 1998 by Oxford University Press
J Singh, R Hamid and BS Reddy
Although epidemiological and experimental studies indicate a strong
relationship between different dietary fats and risk of colon cancer, the
modulating effects of these nutritional factors at the molecular level are
not fully elucidated. Activated ras genes have been implicated in the
etiology of many human malignancies, including colon cancer. It is well
established that the transforming ability of ras-p21 depends on its correct
localization in plasma membrane. We have previously demonstrated that
ingestion of a relatively higher amount of dietary fish oil leads to
reduced plasma membrane levels of ras-p21 with concomitant increase in its
cytoplasmic contents during the promotion and progression phases of
chemically-induced colon tumorigenesis. In this follow-up experiment, we
have found that intake of a high amount of corn oil, one of the most widely
used fats in the American diet, enhances the expression of farnesyl protein
transferase (FPTase). This enzyme catalyses farnesylation of ras precursors
in a critical step during post-translational modification of ras
oncoproteins, thereby enabling their anchorage to plasma membrane. In
contrast, consumption of high amounts of fish oil, which is rich in omega-3
polyunsaturated fatty acids, reduces the levels of FPTase expression, thus
inhibiting post-translational processing of ras precursors resulting in
decreased ras function both in colonic mucosa as well as in colon tumors.
These results correlate with increased incidence and multiplicity of
grossly visibly colon tumors in carcinogen-treated animals fed a high corn
oil diet versus decreased incidence and multiplicity of colon tumors in
their counterparts fed the high fish oil diet. This dietary inhibition of
FPTase may have a practical chemopreventive potential.
ARTICLES
Dietary fish oil inhibits the expression of farnesyl protein transferase and colon tumor development in rodents
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, NY 10595, USA.
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