MOLECULAR REMODELING IN HYPERTROPHIED HEARTS FROM POLYOMAVIRUS LARGE T-ANTIGEN TRANSGENIC MICE

Polyomavirus large T-antigen transgenic mice develop cardiac hypertrop hy characterized by an increase in atrial natriuretic factor and beta- myosin heavy chain isoform expression. The aim of this study was to ex amine changes in proto-oncogene expression in hypertrophied hearts fro m the transgenic mice. Expression of early growth response-1 (Egr-1) m RNA was detected in hearts from all 15 transgenic mice, but was not de tectable in 13 control mice. Reverse transcriptase-polymerase chain re action 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 heart s 3, 17 and 2.8-fold, respectively. Western blots showed an increase i n c-myc, c-jun and ras protein in hypertrophied transgenic hearts. Imm unofluorescence analyses confirmed an increase in Egr-1 and c-jun prot ein in transgenic cardiomyocytes. Proliferating cell nuclear antigen, Ki-ras and HSP 90 mRNAs were decreased 22, 2.7 and 3-fold, respectivel y in the transgenic hearts. Not altered in most hypertrophied hearts w as expression of c-fos, junB, p53, c-neu, c-myc, HSP70, HSP27, TGF-bet a or IGF-1 mRNAs. Proto-oncogene and growth factor gene expression in hypertrophy induced by PVLT expression is modulated, with some proto-o ncogenes increased and others decreased in expression.