Molecular remodelling in hypertrophied hearts from polyomavirus large T-antigen transgenic mice.
Polyomavirus large T-antigen transgenic mice develop cardiac hypertrophy characterized by an increase in atrial natriuretic factor and beta-myosin heavy chain isoform expression. The aim of this study was to examine changes in proto-oncogene expression in hypertrophied hearts from the transgenic mice. Expression of early growth response-1 (Egr-1) mRNA was detected in hearts from all 15 transgenic mice, but was not detectable in 13 control mice. Reverse transcriptase-polymerase chain reaction experiments using Egr-1-specific primers confirmed the increase in Egr-1 mRNA in enlarged hearts from the transgenic mice. Expression of c-jun, junD and Ha-ras mRNAs was increased in the transgenic hearts 3, 17 and 2.8-fold respectively. Western blots showed an increase in c-myc, c-jun and ras protein in hypertrophied transgenic hearts. Immunofluorescence analyses confirmed an increase in Egr-1 and c-jun protein in transgenic cardiomyocytes. Proliferating cell nuclear antigen, Ki-ras and HSP 90 mRNAs were decreased 22, 2.7 and 3-fold, respectively in the transgenic hearts. Not altered in most hypertrophied hearts was expression of c-fos, junB, p53, c-neu, c-myc, HSP70, HSP27, TGF-beta or IGF 1 mRNAs. Proto-oncogene and growth factor gene expression in hypertrophy induced by PVLT expression is modulated with some proto-oncogenes increased and others decreased in expression.
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Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Québe.
Al Moustafa
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Chalifour
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D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D001483:Base Sequence; D006332:Cardiomegaly / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006133:Growth Substances / Q000096:biosynthesis*; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D011519:Proto-Oncogenes; D013312:Stress, Physiological / Q000235:genetics; D015533:Transcriptional Activation; D018631:ras Proteins / Q000096:biosynthesis
D000952:Antigens, Polyomavirus Transforming; D006133:Growth Substances; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D008668:Metallothionein; D018631:ras Proteins