Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma.
Cellular differentiation and mRNA levels of genes involved in kidney growth were investigated in normal kidney cells, cyst-lining epithelial cells of polycystic kidney disease, and renal carcinoma cells (RCC). All cells comparatively studied exhibited an antigenic phenotype of proximal tubular cells as shown by the expression of a panel of brush border membrane enzymes and kidney-associated cell surface antigens. The epithelial developmental antigen Exo-1 was expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and in 20% to 30% of polycystic kidney cells cultured in vitro. Normal kidney cells and RCC were negative under identical culture conditions. The expression of antigen Exo-1 is associated with hyperproliferation in an epithelial tissue compartment composed of cells which have not yet reached their terminal differentiation state. Increased amounts of mRNA of the growth factor receptor system of epidermal growth factor (EGF) receptor and its ligand transforming growth factor (TGF)-alpha were associated with the malignant phenotype of RCC. Increased expression of EGF receptor and TGF-alpha, although less prominent, were also observed in polycystic kidney cells compared with normal kidney cells. In conclusion, the expression of Exo-1 in cyst-lining epithelial cells of autosomal dominant polycystic kidney disease (ADPKD) and the altered regulation of TGF-alpha and EGF receptor in these cells contribute to the hypothesis that hyperproliferation is an underlying pathogenic mechanism of ADPKD.
Klingel
R
R
First Department of Internal Medicine, University of Mainz, Germany.
Dippold
W
W
Störkel
S
S
Meyer zum Büschenfelde
K H
KH
Köhler
H
H
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D004848:Epithelium / Q000276:immunology; D066246:ErbB Receptors / Q000235:genetics; D015870:Gene Expression; D005796:Genes; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology*; D007680:Kidney Neoplasms / Q000235:genetics* / Q000276:immunology*; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000276:immunology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016211:Transforming Growth Factor alpha / Q000235:genetics
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D006133:Growth Substances; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors