Analysis of the factors involved in the retinoic acid-induced differentiation of a retinoid-hypersensitive embryonal carcinoma cell mutant.

Retinoic acid (RA) has been known to play an important role in cellular growth and differentiation as well as in vertebrate development. Many in vitro cell cultures also respond to RA by differentiating. Perhaps the most widely studied of these cultures are embryonal carcinoma (EC) cells. We have used an RA-hypersensitive EC cell mutant, created by retroviral insertion, to analyze the activity of the identifiable components in the RA response pathway. We have analyzed the mRNA expression patterns of the retinoic acid receptors (RARs) alpha, beta, and gamma, the retinoid X receptors (RXRs) alpha, beta, and gamma, and the cellular retinoic acid binding proteins (CRABPs) I and II. Our results indicate that CRABP I, RAR beta, and RAR gamma mRNAs are expressed differentially between parent and RA-hypersensitive mutant cells. All three messages are present at higher basal levels and at earlier times after RA addition in the mutant relative to parental cells. All other elements examined are equivalently expressed. Therefore analyses of the expression patterns of CRABPs, RARs, and RXRs in these RA-hypersensitive cells point to the probable importance of CRABP I, RAR beta, and RAR gamma in the RA induction pathway and also indicate that CRABP II and RXR gamma are not likely to be critical elements in the early differentiative response of cells to RA.