Retinoic acid receptor α 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 RAR alpha agonist Ro 40-6055 completely mimicked the effects of ATRA on growth and transactivation of a beta RAREx2-luciferase reporter construct, while R4R beta- and gamma-specific analogues were ineffective. Furthermore, ATRA-regulated growth and transactivation could be completely blocked by a RAR alpha-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. (C) 1999 Academic Press.