Inhibition of phorbol ester-induced ornithine decarboxylase gene transcription by retinoic acid: a possible mechanism of antitumor promoting activity of retinoids.

We have shown that retinoic acid, applied either to the skin or administered in diet, inhibits skin tumor promotion by TPA. Retinoic acid does not inhibit the initiation step of mouse skin carcinogenesis. Our results indicate that retinoic acid inhibits both stage I and stage II of tumor promotion, and the inhibition of tumor promotion depends upon the duration of retinoic acid treatment. The inhibition of skin carcinogenesis by retinoic acid is not universal; retinoids exhibit specificity towards carcinogens and tumor promoters. In conclusion, the results presented indicate that the inhibition of TPA-induced ODC gene expression may be one of the mechanisms contributing to the antitumor promoting property of the retinoids. However, other mechanisms concerning the effect of retinoic acid on chromatin structure (Porter et al., 1986), glycoprotein synthesis (Levin et al., 1983), peptide growth factors (Sporn et al., 1986), induction of transglutaminase (Lichti and Yuspa, 1985) and the host-immune system (Dennert, 1985) may also explain the molecular basis of retinoid action.