ω-3 and ω-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 ω-3 and ω-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 ω-3 and ω-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 ω-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.