title: Growth regulatory peptide production by human breast carcinoma cells.
abstract: The mechanisms by which human breast cancers regulate their own growth have been studied by us in an in vitro model system. We showed that specific growth factors (IGF-I, TGF alpha, PDGF) are secreted by human breast cancer cells. A variety of experiments suggest that they are involved in tumor growth and progression. These activities are induced by estradiol in hormone-dependent breast cancer cells and secreted constitutively by estrogen-independent cells. Concentrates of conditioned medium derived from breast cancer cells can induce the growth of hormone-dependent cells in vivo in athymic nude mice. Hormone-dependent breast cancer cells also secrete TGF beta. TGF beta is growth inhibitory. Growth inhibitors such as antiestrogens or glucocorticoids increase TGF beta secretion. An antiestrogen-resistant mutant of MCF-7 cells does not secrete TGF beta when treated with antiestrogen, but is growth inhibited when treated with exogenous TGF beta. Thus, TGF beta functions as a negative autocrine growth regulator and is probably responsible for some of the growth inhibitory effects of antiestrogens.
authors.affiliation: Medical Breast Cancer Section, National Cancer Institute, Bethesda, MD 20892.
authors.forename: M E
authors.initials: ME
authors.lastname: Lippman
authors.forename: R B
authors.initials: RB
authors.lastname: Dickson
authors.forename: E P
authors.initials: EP
authors.lastname: Gelmann
authors.forename: N
authors.initials: N
authors.lastname: Rosen
authors.forename: C
authors.initials: C
authors.lastname: Knabbe
authors.forename: S
authors.initials: S
authors.lastname: Bates
authors.forename: D
authors.initials: D
authors.lastname: Bronzert
authors.forename: K
authors.initials: K
authors.lastname: Huff
authors.forename: A
authors.initials: A
authors.lastname: Kasid
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D010452:Peptide Biosynthesis; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D015291:Transforming Growth Factors
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors