Rat ferritin-H: CDNA cloning, differential expression and localization during hepatocarcinogenesis

Elevated serum ferritin levels, especially of the H subunit, accompany many clinical malignancies, By using the subtraction-enhanced display technique, we have recently isolated several cDNA clones which are over-expressed in rat hepatocellular carcinoma induced by diethylnitrosamine, One 830-base-pair clone was 88% similar to human ferritin-a cDNA and encoded a 182 amino acid protein which is 97% homologous to human ferritin-H chain, Hepatic mRNA levels of ferritin-H were increased markedly at the early stage of diethylnitrosamine-induced hepatocarcinogenesis in the rat (6 weeks) and appeared more than 10-fold overexpressed as the tumour progressed, In contrast, hepatic ferritin-H mRNA remained constant during liver regeneration after a 70% partial hepatectomy. lit situ hybridization showed that over-expression of ferritin-H was exclusively localized to preneoplastic foci, to tumour nodules and to tumour cells invading blood vessels, These findings suggest that ferritin-H is a highly conserved protein, its over-expression during tumour development is phenotypically correlated with tumour initiation and/or progression, and it is useful as an early marker for hepatocellular carcinoma.