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c‐ myc amplification in pre‐malignant and malignant lesions induced in rat liver by the resistant hepatocyte model
Author(s) -
Pascale Rosa M.,
De Miglio Maria R.,
Muroni Maria R.,
Simile Maria M.,
Daino Lucia,
Seddaiu Maria A.,
Nufris Alessandra,
Gaspa Leonardo,
Dejana Luca,
Feo Francesco
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960927)68:1<136::aid-ijc24>3.0.co;2-8
Subject(s) - hccs , ecori , southern blot , biology , microbiology and biotechnology , hindiii , dna , hepatocellular carcinoma , pathology , cancer research , restriction enzyme , genetics , medicine
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.