title: Differential proliferative response to linoleate in cultures of epithelial cells from normal human breast and fibroadenomas.
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 phospholipids in mediating the 18:2 omega 6 effect in normal cells. Both normal and fibroadenoma 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.
authors.affiliation: Cancer Research Laboratory, University of California, Berkeley 94720.
authors.forename: A
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: S
authors.initials: S
authors.lastname: Cramer
authors.forename: G K
authors.initials: GK
authors.lastname: Bandyopadhyay
authors.forename: W
authors.initials: W
authors.lastname: Imagawa
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Elias
authors.forename: C W
authors.initials: CW
authors.lastname: Beattie
authors.forename: T K
authors.initials: TK
authors.lastname: Das Gupta
authors.forename: S
authors.initials: S
authors.lastname: Nandi
mesh_terms: D000232:Adenofibroma / Q000473:pathology*; D001940:Breast / Q000166:cytology* / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
chemical_list: D007328:Insulin; D008041:Linoleic Acids; D004815:Epidermal Growth Factor; D002772:Cholera Toxin; D019787:Linoleic Acid; D006854:Hydrocortisone