Retinoic acid receptor alpha mediates growth inhibition by retinoids in human colon carcinoma HT29 cells.
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.
Nicke
B
B
Department of Gastroenterology, Klinikum Benjamin Franklin, Hindenburgdamm 30, Berlin, 12200, Germany.
Kaiser
A
A
Wiedenmann
B
B
Riecken
E O
EO
Rosewicz
S
S
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
D000970:Antineoplastic Agents; D001565:Benzoates; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D013764:Tetrahydronaphthalenes; C068073:Am 580; D014212:Tretinoin; D015474:Isotretinoin