Effect of patient-derived lipids on in vitro expression of oncogenes by ovarian tumor cells.
To understand the role of specific fats on carcinogenesis, we have studied the effects of lipids derived from the ascites fluids of ovarian cancer patients on oncogenic components, associated with the regulation of proliferation. The treatment of tumor cells with patient-derived fats produced increased cell proliferation, as indicated by an increase in the number of S-phase cells. A similar enhancement in cell proliferation was not observed in normal fibroblasts, following lipid treatment. The effects of patient-derived lipids on the expression of c-jun, c-fos, and c-erbB2 gene products were examined. The cellular expression of the proto-oncogene product, c-fos, was increased in all three ovarian tumor cell lines, following lipid treatment. Expression of c-jun gene product was not detected in SKOV-3 or OVCAR-3 and was not induced by fat treatment. UL-1 cells did not express detectable levels of c-jun prior to fat treatment and treatment with patient-derived fat induced significant levels of c-jun product. All three ovarian tumor cell lines expressed the c-erbB2 gene product and it was generally enhanced by treatment with patient-derived lipids. When specific fatty acids were tested, 14:0, 16:1, and 18:1 were principally responsible for the observed enhancement of c-erbB2 levels, while the fatty acids, 18:0 and 20:4, produced the greatest increase in c-fos expression. Many alterations caused by fats are consistent with the loss of normal growth regulation and may account for the epidemiologic link between certain fats and the risk for ovarian cancer.
Gercel-Taylor
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Department of Obstetrics and Gynecology, University of Louisville School of Medicine, Ky., USA.
Taylor
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D001202:Ascitic Fluid / Q000737:chemistry; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000302:isolation & purification / Q000494:pharmacology*; D009857:Oncogenes / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012307:Risk Factors
D008055:Lipids; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human