EXPRESSION OF RETINOIC ACID ALPHA-RECEPTOR AND BETA-RECEPTOR GENES IN LIVER AND HEPATOCELLULAR-CARCINOMA

cDNA probes for human retinoic acid receptors alpha and beta (RAR-alpha and RAR-beta) were modified for use as specific hybridization probes to study hepatocellular carcinomas (HCC) and cell lines, liver regeneration, and fetal development. RAR-beta mRNA was detected at low levels in adult liver and rose markedly during the early phase of liver regeneration. RAR-beta mRNA was present at very low levels in HCC and was not detected in fetal liver. In contrast, RAR-alpha mRNA was present at low levels in normal liver, but showed a marked elevation in several HCCs and cell lines. Growth of cell lines was altered by retinoic acid (RA), but the effects could not be predicted by the levels of either RAR-alpha or RAR-beta mRNA. However, the response correlated with cell phenotype. Three cell lines with an adult phenotype (high albumin and low alpha-fetoprotein) were inhibited by RA, two undifferentiated lines showed moderate growth stimulation, and two of three cell lines that had high levels of alpha-fetoprotein were markedly stimulated by RA.