Control of Specific Messenger RNA Species in Liver and Hepatoma

Summary

Two liver proteins subject to hormonal induction, α2u-globulin and tryptophan oxygenase, were absent from well-differentiated Morris hepatomas. Pulse [³H]-leucine incorporation studies in vivo demonstrated that in Morris hepatoma 5123D no synthesis of α2u-globulin occurs while the host liver synthesizes this protein at a normal rate. Using an in vitro translation system and polyadenylate-containing RNA isolated from host livers or hepatomas, the level of specific mRNA functionally capable of coding for α2u-globulin was determined. Host liver was found to contain α2u-globulin mRNA at normal levels whereas hepatoma tissue was devoid of functionally competent mRNA coding for this protein.

Similarly, levels of specific mRNA coding for tryptophan oxygenase were determined for host livers and hepatomas from control rats and rats administered an inducing dose of hydrocortisone. The hormonal induction of tryptophan oxygenase activity in the host livers was accompanied by a proportionate increase in the level of its mRNA. Tryptophan oxygenase catalytic activity and functional mRNA for this enzyme were undetectable in hepatomas from either control or glucocorticoid-induced animals. The hepatomas contained normal levels of cytoplasmic glucocorticoid receptor that could bind glucocorticoids, undergo normal “activation” and translocate both normal and hepatoma nuclei. Thus, the hepatomas failed to synthesize tryptophan oxygenase due to some pretranslational defect despite the presence of functional glucocorticoid receptor and nuclear binding sites.

The deletion of α2u-globulin and tryptophan oxygenase in these hepatomas is a consequence of a lack of specific mRNA species coding for these two proteins. These findings support the view that hepatomas differ from liver in patterns of gene expression.