Cancer and Metastasis Reviews

, Volume 13, Issue 3, pp 397–410

Cellular proliferation and lipid metabolism: importance of lipoxygenases in modulating epidermal growth factor-dependent mitogenesis

  • Thomas E. Eling
  • Wayne C. Glasgow

DOI: 10.1007/BF00666106

Cite this article as:
Eling, T.E. & Glasgow, W.C. Cancer Metast Rev (1994) 13: 397. doi:10.1007/BF00666106


In this article we have reviewed and discussed the results of our investigation of lipid metabolites as modulators of epidermal growth factor (EGF) signaling pathways. We have studied epidermal growth factordependent mitogenesis in BALB/c 3T3 and Syrian hamster embryo (SHE) cells in culture. We observed that EGF stimulates the formation of prostaglandins in BALB/c 3T3 cells and their formation appears to be necessary for EGF dependent mitogenesis. EGF did not stimulate PGE2 formation in SHE cells and in fact, exogenously added PGE2 inhibited mitogenesis. In both cell lines, EGF stimulated the formation of lipoxygenasederived 13(S)-hydroxyoctadecadienoic acid (13-HODE) and inhibition of 13-HODE formation attenuated mitogenesis. The addition of 13-(S)-HODE enhanced EGF-dependent mitogenesis but when added alone, the compound was not mitogenic. Other metabolites, including lipoxygenase metabolites of arachidonic acid, were either weak simulators of EGF-dependent mitogenesis or essentially inactive. The 13(S)-HODE appears to be formed by an apparently unique lipoxygenase that is regulated by the tyrosine kinase activity of the EGF receptor. The mechanisms by which lipids, particularly the lipoxygenase-derived linoleic acid metabolites, modulate the EGF signaling pathways leading to cell proliferation is discussed. The possible significance of lipoxygenase and prostaglandin H synthase-dependent metabolism of unsaturated fatty acids in breast and colon cancer is also discussed.

Key words

epidermal growth factorprostaglandinslinoleic acidmitogenesissignaling pathwayslipoxygenase

Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Thomas E. Eling
    • 1
  • Wayne C. Glasgow
    • 1
  1. 1.National Institutes of Health, Laboratory of Molecular Biophysics, Eicosanoid Biochemistry SectionNational Institute of Environmental Health SciencesResearch Triangle ParkUSA