Omega-3 and omega-6 fatty acids and PGE2 stimulate the growth of normal but not tumor mouse mammary epithelial cells: evidence for alterations in the signaling pathways in tumor cells.
The direct effect of omega-3 and omega-6 fatty acids on the proliferation of mouse mammary tumor cells (MTC) was examined in a serum-free cell culture system. While the EGF-induced proliferation of normal mammary epithelial cells was shown to be enhanced by omega-3 and omega-6 fatty acids and prostaglandins (PGs), a majority (75-80%) of primary mammary tumors were not stimulated by these agents. Compared to normal cells, some MTC cultures showed a higher susceptibility to inhibition by omega-3 fatty acids. The general lack of response of MTC cultures to PGE2 and cyclic adenosine monophosphate (cAMP) suggests some alterations in the cAMP-mediated pathway. However, the PGE2-induced cAMP levels and cAMP-dependent protein kinase (PKA) activities in the tumor cells were comparable to normal cells. We conclude that the proliferation of mammary tumor cells either follow a cAMP-PKA-independent pathway or have some alterations in the serine/threonine kinase mediated signaling pathway.
McKenzie
K E
KE
Department of Molecular and Cell Biology, University of California at Berkeley 94720.
Bandyopadhyay
G K
GK
Imagawa
W
W
Sun
K
K
Nandi
S
S
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016895:Culture Media, Serum-Free; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D008041:Linoleic Acids; D003994:Bucladesine; D019787:Linoleic Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin