[Mechanism of retinoic acid receptor alpha-mediated growth inhibition of gastric cancer cells by all-trans retinoic acid].

Overview

OBJECTIVE: To study the mechanism of retinoic acid receptor alpha(RAR alpha) in mediating growth inhibition of gastric cancer cells by all-trans retinoic acid(ATRA). METHODS: Expression of RAR alpha was detected by Northern blot. After anti-sense RAR alpha or sense RAR alpha had been transfected into gastric cancer cell lines BGC-823 and MKN-45 respectively, the inhibitory effect of ATRA on cell growth in stable clones was analyzed using MTT assay and colony forming assay in soft agar. The transcriptional activation of retinoic acid response element (RARE) was measured by CAT assay. RESULTS: ATRA could induce expression of RAR alpha in BGC-823 cells, but not in MKN-45 cells. In stable clones, ATRA could inhibit growth of MKN-45 cells transfected with RAR alpha gene, but could not inhibit that of BGC-823 cells transfected with antisense RAR alpha. Transient transfection and CAT assay showed higher beta-RAR response element (beta RARE) transcriptional activation induced by ATRA in MKN-45 cells transfected with RAR alpha compared to parental MKN-45 cells, while lower beta RARE transcriptional activation was seen in BGC cells transfected with antisense RAR alpha gene compared to parental BGC-823 cells. CONCLUSION: Sufficient level of RAR alpha is required for growth inhibition of gastric cancer cells by ATRA.