Expression of alpha-fetoprotein and hepatocyte nuclear factors in rat hepatoma clones: The effect of retinoic acid

Retinoic acid (RA) is involved in regulating cell proliferation and differe ntiation. The effect of RA on the expression of the genes for alpha-fetopro tein (AFP) and other proteins was analyzed in rat hepatoma McA-RH 7777 clon es producing AFP (AFP(+)) or not (AFP(-)). The clones also differed in tran scription of the genes for serum albumin (SA) and hepatocyte nuclear factor s 1 and 4 (HNF1 and HNF4). RA activated transcription of the AFP and SA gen es in both AFP(+) and AFP(-) clones. Induction of AFP synthesis was immunoc hemically detected in only some cells of the AFP(-) clones. Expression of t he HNF1 gene was enhanced in the AFP(-) clones and suppressed in the AFP(+) clone, while the HNF4 gene showed enhanced expression in all clones. It wa s assumed that (i) McA-RH 7777 clones have HNF1-independent pathways of the coordinated induction of the AFP and SA genes, (ii) certain factors mediat e the AFP gene suppression in most AFP(-) clones, and (iii) there are mecha nisms suppressing the HNF1 gene even when the HNF4 gene is activated.