OMEGA-3 AND OMEGA-6 FATTY-ACIDS AND PGE(2) 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 proliferat ion of mouse mammary tumor cells (MTC) was examined in a serum-free ce ll culture system. While the EGF-induced proliferation of normal mamma ry epithelial cells was shown to be enhanced by omega-3 and omega-6 fa tty acids and prostaglandins (PGs), a majority (75-80%) of primary mam mary tumors were not stimulated by these agents. Compared to normal ce lls, some MTC cultures showed a higher susceptibility to inhibition by omega-3 fatty acids. The general lack of response of MTC cultures to PGE(2) and cyclic adenosine monophosphate (cAMP) suggests some alterat ions in the cAMP-mediated pathway. However, the PGE(2)-induced cAMP le vels and cAMP-dependent protein kinase (PKA) activities in the tumor c ells were comparable to normal cells. We conclude that the proliferati on of mammary tumor cells either follow a cAMP-PKA-independent pathway or have some alterations in the serine/threonine kinase mediated sign aling pathway.