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Differential Expression of Insulin-like Growth Factor II mRNA in Human Primary Liver Cancers, Benign Liver Tumors, and Liver Cirrhosis¹

INSERM U75, CHU Necker, Paris 75015, France [E. C., C. L., D. S., B. H., C. B.]; Department of Surgery and Pathology, Hôpital Louise Michel, Evry, France [F. K., D. F.], Department of Biochemistry, University of Massachusetts Medical Center, Worcester, Massachusetts 01605 [M. P. C.]; and the Department of Developmental Biology, Genentech, Inc., South San Francisco, California 94080 [A. U.]

We investigated insulin-like growth factor II (IGF-II) mRNA in three groups of human liver samples including primary liver cancers, benign liver tumors and cirrhosis; indeed these pathological conditions would allow us to distinguish between different steps in liver carcinogenesis.

A 40- to 100-fold increase in IGF-II mRNA was shown in 9/40 of the liver cancer samples as compared to normal adult liver. RNA blot analysis using both IGF-II cDNA and oligonucleotide probes showed the reexpression of two fetal (6 and 5 kilobases) IGF-II transcripts in primary liver cancers and in some cirrhotic adjacent tissues; these included all the samples with enhanced IGF-II expression. By contrast the adult (5.3 kilobases) IGF-II transcript was identified in most of the benign liver tumors and liver cirrhosis; in addition, in some of these samples, the 5-kilobase fetal transcript was also detected. The increase of IGF-II mRNA in some liver cancers is consistent with an autocrine mechanism conferring a selective growth advantage to tumorous liver cells. Furthermore, these results indicate a differential expression of IGF-II transcripts in nonmalignant hepatocyte proliferation (benign liver tumors and cirrhosis) as compared to liver cancer. Finally this study suggests that, in liver cirrhosis and in some benign liver tumors, premalignant proliferative states might be identified by the presence of IGF-II fetal transcripts.

¹ This work was supported by the Association pour la Recherche sur le Cancer (6252) and the Ligue Nationale contre le Cancer.

² Recipient of a fellowship of Fondazione Anna Villa Rusconi. To whom requests for reprints should be addressed, at Unité 75 Biochimie, CHU Necker, 156 rue de Vaugirard, 75015 Paris, France.

Received 5/18/88. Revised 8/16/88. Accepted 8/24/88.

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