DIFFERENTIAL PROLIFERATIVE RESPONSE TO LINOLEATE IN CULTURES OF EPITHELIAL-CELLS FROM NORMAL HUMAN-BREAST AND FIBROADENOMAS

  • 15 February 1989
    • journal article
    • research article
    • Vol. 49  (4) , 857-862
Abstract
Human breast epithelial cells isolated from normal breast tissues of premenopausal women demonstrated direct evidence of a proliferative effect by linoleate (18:2.omega.6) or prostaglandin E2 (PGE2) in the presence of insulin and epidermal growth factor in serum-free cultures within a collagen gel matrix. Neither epidermal growth factor nor 18:2.omega.6 by itself was capable of stimulating growth but together they stimulated proliferation synergistically. Epithelial cells isolated from fibroadenomas on the other hand failed to exhibit any growth stimulation due to 18:2.omega.6 or PGE2. The linoleate-stimulated growth in normal breast epithelial cells was inhibited by indomethacin, a cyclooxygenase inhibitor, which however could be reversed by PGE2. The proliferative response of normal breast epithelial cells to 18:2.omega.6 was accompanied by a greater conversion of [14C]18:2.omega.6 to arachidonic acid and [14C]20:4.omega.6 to prostaglandins than that seen in epithelial cells from fibroadenomas. The turnover of [14C]18:2.omega.6 in the phospholipids of normal cells was higher than in fibroadenomas indicating a possible role of phosholipids in mediating the 18:2.omega.6 effect in normal cells. Both normal and fiboradenoma cells can proliferate in response to cholera toxin and glucocorticoids when supplemented to the insulin- and epidermal growth factor-containing medium. From the results it appears that, unlike normal cells, fibroadenoma cells may have a specific defect in the PGE2-responsive cyclic AMP-generating mechanism whereas cholera toxin-induced mechanism is operative in both types of cells.