Proliferative effects of insulin and epidermal growth factor on mouse mammary epithelial cells in primary culture. Enhancement by hydroxyeicosatetraenoic acids and synergism with prostaglandin E2.

摘要: Linoleate metabolism via the cyclooxygenase pathway enhances proliferation of mammary epithelial cells in serum-free culture presence epidermal growth factor and insulin (Bandyopadhyay, G.K., Imagawa, W., Wallace, D., Nandi, S. (1987) J. Biol. Chem. 262, 2750-2756). Prostaglandin E2 (PGE2) can fully substitute for linoleic acid provided endogenous hydroxyeicosatetraenoic acids (HETEs, lipoxygenase metabolites) are available. The PGE2 effect is partial if activity inhibited by nordihydroguaiaretic acid. Any combination two HETEs out three tested (5-, 12-, 15-HETEs) stimulates synergistically with PGE2; together (i.e. + HETEs), they completely linoleate. In absence PGE2, maximal stimulation cannot be attained HETEs. Exogenous 5-HETE, compared 12- or 15-HETE, preferentially incorporated cells, about 25-30% it retained esterified phospholipids. cellular level nonesterified, free HETE low. Radioimmunoassay revealed that concentrations 15-HETEs media (with without added linoleate) were always higher than 5-HETE. Both intra- extracellular rapidly metabolized cells. Since these capable producing eicosanoids from linoleate, periodic supplementation cultures linoleate allows maintenance levels. Thus, appears not only short-lived cell cultures, but handle 5-HETE differently 15-HETEs. Whatever may pathways interaction, synergism between seems to explain how insulin.