Retinoic acid and 4-hydroxyphenylretinamide induce growth inhibition and tissue transglutaminase through different signal transduction pathways in mouse fibroblasts (NIH 3T3 cells)

4-Hydroxyphenylretinamide (4-HPR) is a synthetic retinoid with minimal toxi city and favorable pharmacokinetics during long-term administration to pati ents in clinical trials, Since 4-HPR binds poorly to the retinoic acid rece ptors, the issue of whether 4-HPR exerts its biological actions via classic al retinoid receptor pathways remains to be resolved. We have previously re ported that stable expression of a truncated retinoic acid receptor alpha, RAR alpha 403, transduced in NIH 3T3 cells by a retroviral vector, rendered the cells resistant to retinoic acid for growth inhibition and induction o f tissue transglutaminase (TGase II). sere, we report that stable expressio n of the dominant negative construct RAR alpha 403 fails to blunt growth in hibition and TGase II induction by 4-HPR, a potent chemopreventive retinoid , in the same cells. These data show that retinoic acid receptors do not me diate either growth inhibition or induction of TGase II activity by 4-HPR i n mouse fibroblast cells.