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

Effects of polyunsaturated fatty acids on expression of early-response genes c-fos and Egr-1 and induction of cell growth were assessed in Swiss 3T3 fibroblasts. Stimulation with arachidonic acid increased mRNA levels of c-fos and Egr-1. This effect was inhibited by preincubation with cyclooxygenase inhibitors and restored by addition of prostaglandin E(2) (PGE(2)), the predominant eicosanoid produced in Swiss 3T3 fibroblasts. Further signaling of PGE(2) 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 PGE(2) also increased cell growth, as determined by uptake of [H-3]-thymidine. In contrast to arachidonic acid, n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) did not increase c-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 PGE(2). In conclusion, our data indicate that AA increases expression of growth-related early genes c-fos and Egr-1 in Swiss 3T3 fibroblasts by its conversion to PGE(2) and subsequent activation of protein kinase C, whereas n-3 fatty acids do not activate this signaling cascade.