Effects of different polunsaturated fatty acids on growth-related early gene expression and cell growth

Effects of polyunsaturated fatty acids on expression of early-response genesc-fos and Egr-1 and induction of cell growth were assessed in Swiss 3T3 fibroblasts. Stimulation with arachidonic acid increased mRNA levels ofc-fos and Egr-1. This effect was inhibited by preincubation with cyclooxygenase inhibitors and restored by addition of prostaglandin E₂ (PGE₂), the predominant eicosanoid produced in Swiss 3T3 fibroblasts. Further signaling of PGE₂ was mediated by a protein kinase C-dependent pathway, since downregulation, or inhibition, of protein kinase C reduced increases in mRNA levels. Parallel to the stimulatory effects on mRNA levels, AA and PGE₂ also increased cell growth, as determined by uptake of ³H]-thymidine. In contrast to arachidonic acid, n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) did not increasec-fos and Egr-1 mRNA levels or cell growth. Furthermore, preliminary data indicate that EPA and DHA even reduce the stimulatory effect of AA, which is associated with reduced formation of PGE₂. In conclusion, our data indicate that AA increases expression of growth-related early genesc-fos and Egr-1 in Swiss 3T3 fibroblasts by its conversion to PGE₂ and subsequent activation of protein kinase C, whereas n-3 fatty acids do not activate this signaling cascade.