MODULATION OF COLON-TUMOR ONCOGENE EXPRESSION BY CANCER PATIENT-DERIVED LIPIDS

In an effort to understand the role of specific fats on carcinogenesis , we have studied the effects of lipids derived from cancer patients o n components associated with the regulation of proliferation. The trea tment of tumor cells with patient-derived fats produced increased cell proliferation, as indicated by shorter doubling times. The effects of patient-derived lipids on the expression of ras, c-jun, c-erbB-2, and p53 gene products were examined. The cellular expression of the ras p roto-oncogene product was increased in both colon tumor cell lines, fo llowing lipid treatment. However, c-jun proto-oncogene expression was elevated in HT-29 cells and appeared unchanged in SK-Co-1 cells after lipid treatment. Treatment of HT-29 tumor cells with patient-derived f ats produced an enhancement of the p53 gene product, whereas fat treat ment reduced p53 expression in SK-Co-1 tumor cells. Further separation of the patient-derived fats indicated that the amplification of p53 g ene expression in HT-29 cells could be achieved primarily by addition of the diacylglycerides fraction. Addition of the purified fatty acids , comprising the diglyceride fraction, indicated that the fatty acids, 16:1, 18:0, and 18:1, induced the most significant increases in p53 e xpression by HT-29 cells. These alterations caused by cancer patient-d erived fats are consistent with the loss of normal growth regulation a nd may explain the epidemiologic association between certain fats and carcinogenesis. (C) 1996 Wiley-Liss, Inc.