High levels of ceruloplasmin in the serum of transgenic mice developing hepatocellular carcinoma

Transgenic mice expressing the Simian virus 40 large T antigen under the co ntrol of the liver-specific human antithrombin-III promoter all develop wel l-differentiated hepatocellular carcinoma. During tumour development serum ceruloplasmin (Cp) increases gradually until it reaches 30 times control le vels in all transgenic mice at 6 months of age. The accumulation of Cp in t he serum is due to the increased transcription of the Cp gene as well as to the increase in Cp mRNA stability in the livers of the transgenic mice. On e-half of the overproduced Cp is charged with copper and Cp-associated seru m oxidase activity increases in parallel with the holo-Cp concentration. Th rough its ferroxidase activity Cp is involved prominently in iron metabolis m. Analysis of copper and iron in serum and liver revealed increased copper levels in the serum of tumour-bearing animals and which increased in paral lel with Cp concentration; the amounts of copper in the liver were unchange d. In contrast, serum iron remained constant during tumour development wher eas the iron concentration in the livers of the transgenic mice decreased.