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-H 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. In 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.
Wu
C G
CG
Department of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.
Groenink
M
M
Bosma
A
A
Reitsma
P H
PH
van Deventer
S J
SJ
Chamuleau
R A
RA
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002273:Carcinogens; D018076:DNA, Complementary / Q000235:genetics*; D004052:Diethylnitrosamine; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D018076:DNA, Complementary; D012333:RNA, Messenger; D004052:Diethylnitrosamine; D005293:Ferritins