title: Retinoic acid receptor alpha mediates growth inhibition by retinoids in human colon carcinoma HT29 cells.
abstract: Although retinoids have been suggested to inhibit chemically induced colon carcinogenesis, the molecular mechanisms underlying retinoid-mediated growth regulation in colon carcinoma cells are unknown. Therefore, we investigated the biological effects of retinoids on growth in HT29 colon carcinoma cells. All-trans retinoic acid (ATRA) treatment of HT29 cells resulted in a profound inhibition of anchorage-independent growth without biochemical or morphological evidence for induction of differentiation. Treatment with the selective RARalpha agonist Ro 40-6055 completely mimicked the effects of ATRA on growth and transactivation of a betaRAREx2-luciferase reporter construct, while RARbeta- and gamma-specific analogues were ineffective. Furthermore, ATRA-regulated growth and transactivation could be completely blocked by a RARalpha-selective receptor antagonist. Thus, ATRA potently inhibits anchorage-independent growth in HT29 cells and this effect is mainly if not exclusively mediated by the retinoic acid receptor alpha.
authors.affiliation: Department of Gastroenterology, Klinikum Benjamin Franklin, Hindenburgdamm 30, Berlin, 12200, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Nicke
authors.forename: A
authors.initials: A
authors.lastname: Kaiser
authors.forename: B
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: E O
authors.initials: EO
authors.lastname: Riecken
authors.forename: S
authors.initials: S
authors.lastname: Rosewicz
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D015870:Gene Expression; D019073:HT29 Cells / Q000473:pathology*; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012176:Retinoids / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001565:Benzoates; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D013764:Tetrahydronaphthalenes; C068073:Am 580; D014212:Tretinoin; D015474:Isotretinoin