Evidence that retinoic acid receptor β induction by retinoids is important for tumor cell growth inhibition

Abstract

Retinoic acid receptor β (RARβ) is thought to be involved in suppressing cell growth and tumorigenicity. Many premalignant and malignant cells exhibit a reduced RARβ expression. However, in some of these cells (e.g. H157 human squamous cell carcinoma cells), RARβ can be induced by retinoids (e.g. all-trans-retinoic acid, ATRA) because its promoter contains a retinoic acid response element. To examine the hypothesis that RARβ induction is important for inhibition of cell proliferation by retinoids, we blocked ATRA-induced RARβ expression in H157 cells using a retroviral vector harboring multiple copies of antisense RARβ2 sequences. Antisense RARβ- transfected cells showed not only decreased expression of ATRA-induced RARβ protein but also reduced ATRA-induced RARE binding activity and transactivation. Importantly, all antisense RARβ transfectants of H157 cells were less responsive than vector-transfected cells to the growth inhibitory effects of the retinoids ATRA and Ch55 in vitro. These results demonstrate that RARβ induction may play an important role in mediating growth inhibitory effects of retinoids in cancer cells.