title: Proliferation of Shionogi carcinoma 115 cells by glucocorticoid-induced autocrine heparin-binding growth factor(s) in serum-free medium.
abstract: Shionogi carcinoma 115 (SC115) has been accepted for 20 years as an androgen-responsive mouse mammary tumor. Recently, the growth of the tumor was also found to be stimulated by pharmacological, but not physiological, doses of glucocorticoid. In a serum-free culture system [Ham's F-12:Eagle's minimal essential medium (1:1, v/v) containing 0.1% bovine serum albumin], we have established that 10(-8) M testosterone, or 10(-6) M dexamethasone significantly stimulates the growth of SC-3 cells (a cloned cell line from a SC115 tumor) via androgen and glucocorticoid receptors, respectively. Recently, we demonstrated that the testosterone-induced growth of SC-3 cells is mediated through autocrine fibroblast growth factor (FGF)-like peptide(s). In the present study, mechanisms of glucocorticoid-induced growth of SC-3 cells were investigated. Serum-free conditioned medium obtained from 10(-6) M dexamethasone-stimulated SC-3 cells was fractionated by heparin-Sepharose affinity chromatography; one sharp peak of growth-stimulatory activity for SC-3 cells, eluted at 1.3 M NaCl, was identified. When the peak fraction was added to serum-free medium, the shape of SC-3 cells changed from an epithelial to a fibroblast-like appearance, similar to that induced with testosterone or basic (b)FGF. Furthermore, the growth-stimulatory activity induced with the peak fraction as well as testosterone or bFGF was markedly inhibited by anti-bFGF antibody immunoglobulin G (75 to 90% inhibition was obtained), and the specific binding of 125I-bFGF on SC-3 cells was significantly inhibited by the peak fraction. These results suggest that the glucocorticoid-induced growth of SC-3 cells is also mediated through FGF-like peptide(s) in an autocrine mechanism, which is very similar to that induced by testosterone, if not identical.
authors.affiliation: Department of Pathology, Osaka University Medical School, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamanishi
authors.forename: N
authors.initials: N
authors.lastname: Nonomura
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: N
authors.initials: N
authors.lastname: Terada
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: B
authors.initials: B
authors.lastname: Sato
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000494:pharmacology; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D017468:Receptors, Fibroblast Growth Factor; D011975:Receptors, Mitogen / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D013739:Testosterone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D003470:Culture Media; D007074:Immunoglobulin G; D017468:Receptors, Fibroblast Growth Factor; D011975:Receptors, Mitogen; D013739:Testosterone; D005346:Fibroblast Growth Factors; D003907:Dexamethasone; D040262:Receptors, Vascular Endothelial Growth Factor