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Journal of Histochemistry and Cytochemistry, Vol. 48, 1601-1608, December 2000, Copyright © 2000, The Histochemical Society, Inc.

ARTICLE

Expression of the Membrane-associated Carbonic Anhydrase Isozyme XII in the Human Kidney and Renal Tumors

Seppo Parkkilaa,b, Anna-Kaisa Parkkilaa,c, Juha Saarniod, Jyrki Kiveläa,f, Tuomo J. Karttunene, Kari Kaunistoa, Abdul Waheedg, William S. Slyg, Özlem Türecih, Ismo Virtaneni, and Hannu Rajaniemia
a Departments of Anatomy and Cell Biology, University of Oulu, Oulu, Finland
b Clinical Chemistry, University of Oulu, Oulu, Finland
c Neurology, University of Oulu, Oulu, Finland
d Surgery, University of Oulu, Oulu, Finland
e Pathology, University of Oulu, Oulu, Finland
f Parolannummi Garrison Hospital, Hattula, Finland
g Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, MO
h Department of Internal Medicine, University of Saarland, Homburg, Germany
i Department of Anatomy, Institute of Biomedicine, University of Helsinki, Helsinki, Finland

Correspondence to: Seppo Parkkila, Dept. of Anatomy and Cell Biology, Box 5000, FIN-90014 University of Oulu, Finland. E-mail: seppo.parkkila@oulu.fi

Carbonic anhydrase isozyme XII (CA XII) is a novel membrane-associated protein with a potential role in von Hippel–Lindau carcinogenesis. Although Northern blotting has revealed positive signal for CA XII in normal human kidney, this is the first study to demonstrate its cellular and subcellular localization along the human nephron and collecting duct. Immunohistochemistry with a polyclonal antibody (PAb) raised against truncated CA XII revealed distinct staining in the basolateral plasma membrane of the epithelial cells in the thick ascending limb of Henle and distal convoluted tubules, and in the principal cells of the collecting ducts. A weak basolateral signal was also detected in the epithelium of the proximal convoluted tubules. In addition to the normal kidney specimens, this immunohistochemical study included 31 renal tumors. CA XII showed moderate or strong plasma membrane-associated expression in most oncocytomas and clear-cell carcinomas. The segmental, cellular, and subcellular distribution of CA XII along the human nephron and collecting duct suggests that it may be one of the key enzymes involved in normal renal physiology, particularly in the regulation of water homeostasis. High expression of CA XII in some renal carcinomas may contribute to its role in von Hippel–Lindau carcinogenesis.

(J Histochem Cytochem 48:1601–1608, 2000)

Key Words: aquaporin-2, cancer, carbonic anhydrase, carcinoma, immunohistochemistry, kidney, plasma membrane


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