Modulation of phorbol ester-associated events in epidermal cells by linoleate and arachidonate |
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Authors: | Martha A Belury Mary Locniskar Susan M Fischer |
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Affiliation: | (1) Division of Nutrition, The University of Texas at Austin, 78712 Austin, Texas;(2) Research Division, The University of Texas M.D. Anderson Cancer Center, Science Park, P.O. Box 389, 78957 Smithville, TX |
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Abstract: | To elucidate the events elicited by the skin tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA), which are modulated by linoleic acid (LA) and arachidonic acid (AA), the activity
of these fatty acids in cultured mouse epidermal cells was compared. Approximately 94% of either exogenous radiolabelled fatty
acid was incorporated into the total phospholipid pool over 15 h. The relative distribution among the phospholipid classes
differed, however, such that approximately 70% of phospholipid-associated 14C]-LA was found in phosphatidylcholine, compared to approximately 30% for 14C]AA. Phosphatidylethanolamine and phosphatidylinositol/phosphatidylserine contained 17 and 13% of the phospholipid 14C]LA, and 34 and 30% of 14C]AA, respectively. Prostaglandin (PG) E2 production was low but similar in unstimulated cultures prelabelled with either 14C]LA or 14C]AA. However, in cultures treated with TPA (1.6 μM), 14C]AA-prelabelling resulted in approximately three times the amount of 14C]PGE2 compared with cultures prelabelled with 14C]LA. Cultured cells were found to contain significant δ6 desaturase activity, which may enable conversion of LA to AA, and
thus may account for the observed PGE2 production from 14C]LA treated cells. AA-Supplemented (1.6 μM) cultures supported approximately twice the induction of ornithine decarboxylase
activity by TPA compared with cultures treated with 1.8 μM LA. Activation of partially purified protein kinase C was similar
for either fatty acid tested over a 10–300 μM dose range. Overall, the results suggest that LA does not have the same biological
activity as AA with regard to several TPA-associated events known to be important in skin tumor promotion. This reduced biological
activity of LA may be partly responsible for the known inhibition of mouse skin tumor promotion by high dietary levels of
LA Leyton, J., Lee, M.L., Locniskar, M.F., Belury, M.A., Slaga, T.J., Bechtel, D., and Fischer, S.M. (1991)Cancer Res. 51, 907–915]. |
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