Pretranslational control of tryptophan oxygenase levels in Morris hepatoma and host liver.
Tryptophan oxygenase is present and hormonally inducible in host livers but is absent in transplanted Morris hepatomas examined under basal conditions as well as in hormonally induced animals. Studies were performed to determine whether the absence of tryptophan oxygenase in hepatomas is mediated by an alteration in the translational efficiency or the level of the messenger RNA (mRNA) for tryptophan oxygenase. The tissue level of the specific mRNA coding for tryptophan oxygenase was quantitated in an mRNA-dependent Krebs ascites cell-free protein-synthesizing system. The enzyme levels and mRNA activities in host livers and hepatomas from control rats and rats given injections of an inducing dose of hydrocortisone were compared; they indicate that the induction of tryptophan oxygenase in host livers by hormones is accompanied by a proportional increase in the level of its mRNA, whereas in the transplanted hepatomas the tryptophan oxygenase catalytic activity and the mRNA coding for this enzyme were undetectable in both control and glucocorticoid-induced animals. No functional mRNA for tryptophan oxygenase could be detected in the total polyadenylate-containing mRNA isolated from the Morris hepatoma cells. The hepatomas contained normal levels of cytoplasmic glucocorticoid receptor that could bind glucocorticoid, undergo "activation," and translocate to both normal and neoplastic nuclei. Thus, deletion of tryptophan oxygenase in hepatomas is a consequence of the absence of the gene product, i.e., the tryptophan oxygenase mRNA, which codes for its synthesis; this is not due to detectable alterations in the ability of the glucocorticoid receptor to bind the steroid hormone, or of the hormone-receptor complex to undergo activation, or of the activated steroid-receptor complex to bind to nuclei derived from the hepatoma or normal liver.
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004790:Enzyme Induction; D006854:Hydrocortisone / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011956:Receptors, Cell Surface; D014366:Tryptophan Oxygenase / Q000096:biosynthesis*
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D004247:DNA; D014366:Tryptophan Oxygenase; D006854:Hydrocortisone