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

Autor: Maria Rosaria Muroni, Maria Maddalena Simile, A. Nufris, Maria Antonietta Seddaiu, Rosa Maria Pascale, Maria Rosaria De Miglio, Lucia Daino, Luca Dejana, Leonardo Gaspa, Francesco Feo
Rok vydání: 1996
Předmět:
Zdroj: International Journal of Cancer. 68:136-142
ISSN: 1097-0215
0020-7136
DOI: 10.1002/(sici)1097-0215(19960927)68:1<136::aid-ijc24>3.0.co;2-8
Popis: 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. Southern-blot analysis of EcoRI-restricted DNA from normal liver, early and late adenomas, 12 weeks (EAs) and 30 weeks (LAs) after initiation, and HCCs, showed 2 bands of 18 and 3.2 kb hybridizing with c-myc, in all tissues. c-myc amplification occurred in almost all HCCs, and in the majority of EAs and LAs. These results were confirmed by dilution analysis. c-myc amplification was also seen in adenomas and HCCs by Southern analysis with HindIII-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 HindIII-restricted DNA from HCCs, but not in normal liver and adenomas, and a 7.1-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 β-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 suggest a role of c-myc rearrangement in the progression of adenomas to malignancy. © 1996 Wiley-Liss, Inc.
Databáze: OpenAIRE
Externí odkaz: