c-myc amplification in pre-malignant and malignant lesions induced in rat liver by the resistant hepatocyte model

✍ Scribed by Rosa M. Pascale; Maria R. De Miglio; Maria R. Muroni; Maria M. Simile; Lucia Daino; Maria A. Seddaiu; Alessandra Nufris; Leonardo Gaspa; Luca Dejana; Francesco Feo

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 968 KB
• Volume: 68
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19960927)68:1<136::aid-ijc24>3.0.co;2-8

✦ Synopsis

We have investigated by restriction fragment analysis genomic abnormalities involving the c-myc gene in DNA isolated from adenomas and hepatocellular carcinomas (HCCs). Adenomas and HCCs were induced by the "resistant hepatocyte" protocol in diethylnitrosamine-initiated male F344 rats. Southem-blot analysis of EcoRI-restricted DNA from normal liver, early and late adenomas, I 2 weeks (EAs) and 30 weeks (Us) after initiation, and HCCs, showed 2 bands of 18 and 3.2 kb hybridizing with c-myc, in all tissues. c-rnyc amplification occurred in almost all HCCs, and in the majority of EAs and Us. These results were confirmed by dilution analysis. c-myc amplification was also seen in adenomas and HCCs by Southem analysis with Hindlll-restricted DNA, and in HCCs by differential PCR. c-myc mRNA increase occurred in all adenomas and HCCs, but it was higher in the lesions showing gene amplification. Moreover, a 13-kb DNA extraband, hybridizing with c-myc, was found in the Hindlll-restricted DNA from HCCs, but not in normal liver and adenomas, and a 7. I -kb extra band was present in EcoRI-digested DNA from one LA EcoRI-restricted DNA from some adenomas exhibited a decrease in intensity of the 18-kb fragment, and an increase in intensity of the 3.2-kb fragment. No alteration in banding pattern occurred in the B-actin gene in adenomas. These results provide evidence of amplification and some other rearrangements involving the c-myc gene, in pre-malignant and malignant liver lesions, induced by the RH protocol. and suaest a role of c-myc rearraniement inthe prog-mion of adenoias to malignancy.