Cloning and characterization of a novel retinoid-inducible gene 1(RIG1) deriving from human gastric cancer cells

Retinoids exert wide-spectrum anti-tumor activities, which are mediated via the induction of growth arrest, differentiation or apoptosis. To determine whether the effects of retinoids are mediated by specific gene activation or repression, SC-M1 CL23 gastric cancer cells, pretreated with either vehi cle alone or all-trans retinoic acid (10 mu M) for 1 day, were analyzed usi ng the technique of differential display. A novel retinoid-inducible gene 1 (RIG1) was isolated. The full-length RIG1 cDNA contained 768 base pairs an d encoded a protein of 164 amino acids with a molecular weight of 18 kDa. T he RIG1 gene was ubiquitously expressed in normal tissue, and its expressio n was positively associated with cellular density. Nucleotide sequence anal ysis demonstrated that the RIG1 gene was similar to a recently-isolated TIG 3 gene, and displayed 54% nucleotide sequence homology with a type II tumor suppressor gene H-REV107-1. RIG1 cDNA, however, contained an extra 32 base pairs located at its 5' end and revealed three base pair differences for t he remaining sequences leading to two amino acids substitution between the two encoded proteins. All-trans retinoic acid increased the level of RIG1 m RNA in a time- and concentration-dependent manner in SC-M 1 CL23 gastric ca ncer cells. This was not observed for the H-REV-107-1 gene. The RIG1 regula tion was related to cellular retinoid sensitivity. Both retinoic acid recep tor alpha- and retinoic acid receptor gamma-selective agonists increased RI G1 mRNA level, and the retinoid x receptor-selective agonist potentiated th is regulation. In conclusion, the cDNA of a novel retinoid-inducible gene R IG1 has been cloned. This gene is regulated by retinoic acid through the he terodimer of retinoic acid receptor and retinoid x receptor. (C) 2000 Elsev ier Science Ireland Ltd. All rights reserved.