Elevated c-myc protooncogene expression in autosomal recessive polycystic kidney disease.
The polycystic kidney diseases (PKDs) are a group of disorders characterized by the growth of epithelial cysts from the nephrons and collecting ducts of kidney tubules. The diseases can be inherited or can be provoked by environmental factors. To investigate the molecular basis of the abnormal cell growth associated with PKD, c-myc protooncogene expression was studied in a mouse model for autosomal recessive PKD. Homozygous recessive C57BL/6J (cpk/cpk) mice develop massively enlarged cystic kidneys and die from renal failure shortly after 3 weeks of age. Quantitative dot blot and RNA blot hybridization experiments in which whole kidney poly(A)+ RNA was hybridized with a c-myc RNA probe showed a 2- to 6-fold increase in c-myc mRNA at 2 weeks, and a 25- to 30-fold increase in c-myc mRNA at 3 weeks of age in polycystic mice, as compared to normal littermates. c-myc expression was also examined under two conditions in which kidney cell growth was experimentally induced in normal adult mice: compensatory renal hypertrophy and tubule regeneration following folic acid-induced renal cell injury. While compensatory hypertrophy resulted in only a small (less than 3-fold) increase in c-myc, folic acid treatment gave rise after 24 hr to a 12-fold increase in c-myc mRNA. The induction of c-myc by folic acid is consistent with increased cellular proliferation in regenerating tubules. In contrast, polycystic kidneys show only a minimal increase in cellular proliferation over that seen in normal kidneys, while c-myc levels were found to be markedly elevated. Thus, the level of c-myc expression in cystic kidneys appears to be out of proportion to the rate of cell division, suggesting that elevated and potentially abnormal c-myc expression may be involved in the pathogenesis of PKD.
D000367:Age Factors; D000818:Animals; D005786:Gene Expression Regulation; D005808:Genes, Recessive; D006657:Histones / Q000235:genetics; D007668:Kidney / Q000502:physiology; D051379:Mice; D007690:Polycystic Kidney Diseases / Q000235:genetics*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D012038:Regeneration
D006657:Histones; D012333:RNA, Messenger