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Steady‐state levels of the mitochondrial (mt) mRNA encoding subunit II of cytochrome oxidase (COII) were increased 5‐10 fold in fully transformed cell lines derived from rodent embryonic fibroblasts after transfer of polyoma virus DNA, and in immortalized cell lines established by transfer of plt (polyoma large T protein), E1A (adenovirus) and myc oncogenes. Increased mitochondrial gene expression was not related with active growth per se: it was low in fast‐growing rat embryo cells, and it did not change upon serum starvation and subsequent stimulation of FR3T3 cells. The number of copies of mtDNA did not vary, and different mitochondrial mRNAs and rRNAs were increased in the same proportions, suggesting a change in the rate of accumulation of their common precursor.

GHR‐P63 (‘growth hormone‐regulated protein of 63,000 daltons’) is an acidic glycoprotein secreted by rat hepatocytes whose synthesis is abolished upon hypophysectomy. The sequence of its mRNA including the entire coding and 3′ untranslated regions was determined from a nearly full‐length lambda gt11‐cDNA clone. The sequence contained two ATGs in frame giving rise to two overlapping coding regions which could encode precursor polypeptides of 416 and 406 amino acid residues (MrS = 46549 and 45371). These potential translation initiation codons appeared to be functional both in vitro and in intact cells since two precursors of the correct size were immunoprecipitated as products of mRNA translation. The unglycosylated precursors were converted into intermediate intracellular forms of about 56,000 daltons containing N‐linked oligosaccharide side chains and thereafter into the secretory form of approximately equal to 63,000 daltons. Strong sequence homologies, both at the nucleotide and the amino acid levels were found between GHR‐P63 and several serum protease inhibitors, more particularly mouse contrapsin and human alpha 1‐antichymotrypsin. In agreement with sequence data, GHR‐P63 purified from rat blood by affinity chromatography was found to carry an anti‐trypsin activity. GHR‐P63 mRNA, virtually undetectable in hepatocytes from hypophysectomized rats, could be hormonally re‐induced to subnormal levels both in vivo by treating animals with hormones and in vitro by incubating the defective cells with hormones. Growth hormone was absolutely required but had a weak effect when used alone. Glucocorticoids which had no effect per se, strongly potentiated the action of growth hormone. Nuclear run‐off experiments suggest that hormones regulated GHR‐P63 mRNA levels by acting mostly, if not exclusively, on gene transcription.

We have isolated and sequenced a cloned cDNA corresponding to an mRNA present in significantly higher levels in rat cells transformed by polyoma virus, Rous sarcoma virus, and the cellular oncogene H‐ras than in the normal parental cell lines. The mRNA transcript is also rapidly induced by the polypeptide growth factor epidermal growth factor, providing a new link between oncogenes and growth factors. Both the growth factor and the oncogenes control expression of the corresponding gene at the transcriptional level. Our results point to the existence of intracellular mechanisms that are common to the action of both growth factors and oncogenes.