Role of polyunsaturated fatty acids as signal transducers: amplification of signals from growth factor receptors by fatty acids in mammary epithelial cells.
The growth, morphogenesis and differentiation of milk producing epithelial tissues in the developing mammary glands require interaction with extracellular matrices and stimulation by hormones, growth factors and essential fatty acids. In primary culture, the proliferation of mammary epithelial cells (MEC), induced by epidermal growth factor (EGF), is enhanced and sustained by linoleate and its eicosanoid metabolites. Since a combination of linoleic acid (18:2 omega 6) and prostaglandin E2 or cAMP has synergistic effect on EGF-stimulated growth, it is suggested that additional cAMP-dependent protein kinase A (PK-A) independent pathways may also contribute to the linoleate effect on EGF action. Possible involvement of Ca2+/phospholipid-dependent protein kinase C (PK-C) is explored. Both linoleate and arachidonate can activate Type-II and Type-III protein kinase-C in MEC and a PK-C inhibitor can block growth stimulation by EGF and fatty acids. Like 12-O-Tetradecanoly phorbol-13-acetate (TPA), a PK-C activator which also enhances EGF-stimulated growth of MEC, linoleate can phosphorylate a 40-42 KD protein. EGF itself can stimulate transient phosphorylation of the same protein in MEC cultures but when supplemented with linoleate, which does not influence the ligand binding affinity of EGF-receptors, the transient phosphorylation signal in 40-42 KD protein is sustained.(ABSTRACT TRUNCATED AT 250 WORDS)
Bandyopadhyay
G K
GK
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Hwang
S
S
Imagawa
W
W
Nandi
S
S
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004041:Dietary Fats / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects; D066246:ErbB Receptors / Q000187:drug effects / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000502:physiology*; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated; D007527:Isoenzymes; D008041:Linoleic Acids; D016718:Arachidonic Acid; D004815:Epidermal Growth Factor; D019787:Linoleic Acid; D066246:ErbB Receptors; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate