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Differential Regulation of Normal and Tumor ₁-Fetoprotein Genes in Fetal Hepatocyte x Hepatoma Hybrids¹

Le Centre de Recherche en Cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Québec, Canada G1R 2J6 [M-C. G., B. T., L. B.], and Département de Biologie Moléculaire, Université Libre de Bruxelles, B1640 Rhode-St-Genèse, Belgique [J. S., C. S.]

Fetal rat hepatocytes and mouse hepatoma cells actively expressing ₁-fetoprotein (AFP) and albumin genes were fused with the use of Sendal virus, and the expression of normal (rat) and tumor (mouse) AFP and albumin genes was analyzed in hybrid clones. The tumor AFP gene and both albumin genes were active in 103 hybrids. Expression of the normal fetal rat AFP gene, however, was maintained in only 3 hybrids, and it was frequently lost or decreased selectively upon subcloning. Furthermore, the normal AFP gene, when expressed, was more reactive than the tumor AFP gene to repression by a glucocorticosteroid hormone. These results suggest constitutive differences in the manner an oncofetal gene is activated and regulated in normal and neoplastic states. AFP gene expression in normal hepatocytes appears to be subordinated to a differentiation program degenerated and bypassed in hepatoma cells.

¹ Supported by a grant from the Medical Research Council of Canada and by contracts between the Université Libre de Bruxelles and the Belgian Government (Actions de Recherche Concertées and the Belgian Caisse Générale d'Epargne et de Retraite).

² Supported by a studentship from Le Fonds de la Recherche en Santé du Québec.

³ To whom requests for reprints should be addressed.

⁴ A senior research associate of the Belgian Fonds National de la Recherche Scientifique.

Received 4/15/88. Revised 8/ 5/88. Accepted 8/11/88.