E. V. Varga, I. F. Kustova, and N. L. Lazarevich
Institute of Carcinogenesis, Blokhin Cancer Research Center,
Russian Academy of Medical Sciences, Moscow, 115478 Russia
Received December 29, 1997; in final form, August 10, 1998
AbstractRetinoic acid (RA) is involved in regulating cell proliferation and differentiation. The effect of RA
on the expression of the genes for
-fetoprotein (AFP) and other proteins was analyzed in rat hepatoma
McA
RH 7777 clones producing AFP (AFP+) or not (AFP). The clones also differed in transcription of the
genes for serum albumin (SA) and hepatocyte nuclear factors 1 and 4 (HNF1 and HNF4). RA activated tran-
scription of the AFP and SA genes in both AFP+ and AFP clones. Induction of AFP synthesis was immu-
nochemically detected in only some cells of the AFP clones. Expression of the 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 was assumed that (i) McA-RH 7777 clones have HNF1-independent pathways of the coordinated
induction of the AFP and SA genes, (ii) certain factors mediate the AFP gene suppression in most AFP clones,
and (iii) there are mechanisms suppressing the HNF1 gene even when the HNF4 gene is activated.
Key words: hepatoma, retinoic acid,
-fetoprotein, albumin, hepatocyte nuclear factors
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