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 growt h regulation in colon carcinoma cells are unknown. Therefore, we investigat ed the biological effects of retinoids on growth in HT29 colon carcinoma ce lls. All-trans retinoic acid (ATRA) treatment of HT29 cells resulted in a p rofound inhibition of anchorage-independent growth without biochemical or m orphological evidence for induction of differentiation. Treatment with the selective RAR alpha agonist Ro 40-6055 completely mimicked the effects of A TRA on growth and transactivation of a beta RAREx2-luciferase reporter cons truct, while R4R beta- and gamma-specific analogues were ineffective. Furth ermore, ATRA-regulated growth and transactivation could be completely block ed by a RAR alpha-selective receptor antagonist, Thus, ATRA potently inhibi ts anchorage-independent growth in HT29 cells and this effect is mainly if not exclusively mediated by the retinoic acid receptor alpha. (C) 1999 Acad emic Press.