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Cellular Expression of -Fetoprotein Gene and Its Relation to Albumin Gene Expression during Rat Azo-Dye Hepatocarcinogenesis¹

Laboratoire de Biologie Cellulaire and Unité INSERM U24, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France

During hepatocarcinogenesis, -fetoprotein (AFP) synthesis may be dramatically increased while albumin synthesis is frequently decreased. Therefore, a reciprocal modulation between both gene expressions has been hypothesized. In this work, we combined in situ hybridization and immunoperoxidase on parallel liver tissue sections in order to analyze at the cellular level, AFP gene expression and its relation to ALB gene expression in both early and neoplastic lesions induced by 3MeDAB in the rat. In early lesions, cell populations were heterogeneous as regards AFP expression. High levels of AFP transcripts were detected both in oval type cells and in a subset of basophilic hepatocytes within preneoplastic lesions. In these two highly AFP-expressing cell populations, significant levels of ALB transcripts were concomitantly detected. In the majority of altered hepatocytes, no AFP expression was detected while the level of ALB expression was decreased. In neoplastic lesions, AFP expression was strikingly heterogenous and independent from the degree of morphological differentiation. No evidence of reciprocal modulation with ALB gene expression could be assessed. In both preneoplastic and neoplastic lesions, a few altered hepatocytes displayed significant levels of AFP transcripts while no corresponding protein could be detected; such a discrepancy was not observed for ALB. This work shows that during 3MeDAB hepatocarcinogenesis, AFP gene activation occurs in heterogenous cell populations and according to different cellular patterns. Our observations lend no support to the hypothesis of a reciprocal modulation between AFP and ALB gene expressions during rat azo-dye hepatocarcinogenesis.

¹ This work was supported in part by the Fonds pour la Recherche Médicale and the Conseil Scientifique, Faculté de Médecine Xavier Bichat, Université Paris VII.

² To whom reprint requests should be addressed at Laboratorie de Biologie Cellulaire, Faculté de Médecine Xavier Bichat, 16, rue Henri Huchard, 75018 Paris, France.

Received 5/10/88. Revised 10/ 3/88. Revised 12/30/88. Accepted 1/ 6/89.