C-fos expression is hypersensitive to serum-stimulation in cultured cystic kidney cells from the C57BL/6J-cpk mouse.
Cystic kidneys of the C57BL/6J-cpk murine model of polycystic kidney disease show a marked overexpression of the proto-oncogenes c-fos, c-myc, and c-Ki-ras, consistent with an increased rate of cell proliferation and an altered state of differentiation. To determine if cystic cells have increased responsiveness to stimulation with mitogenic agents, quiescent primary cultures from normal and cystic cpk kidneys were treated with fetal bovine serum (FBS), 8-bromo-cAMP (cAMP), or epidermal growth factor (EGF). The level of c-fos induction following stimulation by FBS was found to be dramatically higher in cystic cells than in normal cells; whereas induction by cAMP or EGF was essentially the same in both cell types and much less than that seen in FBS-stimulated cells. To determine if this serum hypersensitivity reflects an increased proliferative state in vivo, c-fos induction was examined in cultures derived from normal kidneys stimulated to regenerate by folic acid-induced acute renal injury. As with cystic kidneys, the folic acid-injured kidneys showed increased c-fos responsiveness to FBS in cell culture. These experiments suggest that cystic and regenerating kidneys have an altered phenotypic state in vivo that is manifested in cell culture by serum hypersensitivity. However, whereas the folic acid-injured kidneys ultimately reestablish normal kidney function, cystic kidneys further progress to renal failure, suggesting that cystic epithelial cells are locked in this altered state of differentiation.
Rankin
C A
CA
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66160.
Grantham
J J
JJ
Calvet
J P
JP
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001769:Blood; D002455:Cell Division; D002478:Cells, Cultured; D003470:Culture Media; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005492:Folic Acid / Q000494:pharmacology; D005786:Gene Expression Regulation; D016762:Genes, fos; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D052177:Kidney Diseases, Cystic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D003470:Culture Media; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004815:Epidermal Growth Factor; D005492:Folic Acid