title: Retinoic acid and 1,25-dihydroxyvitamin D3 inhibit tenascin-C expression in rat glioma C6 cells.
abstract: Tenascin-C (Tn-C) is an extracellular matrix protein with growth-, invasive-, and angiogenesis-promoting activities. Tn-C is upregulated during wound healing, tumorigenesis, and other pathological conditions. Highly malignant gliomas with poor prognosis exhibit high levels of Tn-C expression. Here we demonstrate that Tn-C RNA expression in glioma C6 cells is inhibited in a dose-dependent manner by retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-D3). No additive or synergistic effects were found. Inhibition is maximum 24 hr after RA or 1,25-D3 treatment, prior to a delayed cytotoxic effect starting at day 4-5 of treatment, and correlates with a reduction in the synthesis of Tn-C protein. Tn-C expression is also inhibited, but to a lesser extent by prostaglandin D2 (PGD2). Furthermore, both RA and 1,25-D3, but not PGD2 abolish the induction of Tn-C by the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate. The inhibition of Tn-C expression might be relevant for the anti-cancer activity of RA and 1,25-D3.
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Alvarez-Dolado
authors.forename: J M
authors.initials: JM
authors.lastname: González-Sancho
authors.forename: C
authors.initials: C
authors.lastname: Navarro-Yubero
authors.forename: L F
authors.initials: LF
authors.lastname: García-Fernández
authors.forename: A
authors.initials: A
authors.lastname: Muñoz
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015230:Prostaglandin D2 / Q000494:pharmacology; D051381:Rats; D018167:Receptors, Calcitriol / Q000235:genetics; D019063:Tenascin / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D002273:Carcinogens; D018167:Receptors, Calcitriol; D019063:Tenascin; D014212:Tretinoin; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2