Abstract
Tankyrase, which functions at telomeres and other cellular compartments, is thought to be a positive regulator of telomerase; its isoenzyme tankyrase 2 has been cloned as a putative cancer antigen. This pilot immunohistochemical study was designed to examine whether tumors overexpress tankyrase 2. An antibody was generated by using synthetic peptide specific for tankyrase 2 and was tested by Western blot and immunocytochemically; no cross-reaction with isoenzyme 1 was revealed. Among tissue sections, two tumors of 18 specimens were positive for tankyrase 2. Others were negative or contained barely detectable protein. The surrounding normal tissues were negative. Tankyrase 2 was also revealed in epithelial cells of a limited number of normal renal tubules, whereas other renal tissues were negative. These data suggest that tankyrase 2 is not expressed ubiquitously in human tissues. To determine whether the up-regulation of tankyrase 2 is associated with tissue regeneration and cell proliferation, we compared the activity and concentration of the enzyme in a model human embryonic kidney cell line 293 arrested by serum deprivation and restimulated with serum. The serum-starved quiescent cell culture exhibited detectable protein as did the proliferating cells; enzyme activity dramatically increased in the latter. We conclude that pathologic overexpression of tankyrase 2 in some tumors may be a result of the cancer-related adaptation of the malignant cells dependent on tankyrase activity. Under normal conditions, the protein might be up-regulated during cell differentiation and also posttranslationally in proliferating cells.
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Acknowledgements
The authors express their thanks to M. Mogilnikov and I. Skulachev (A.N. Belozersky Institute, Moscow State University) for their help with the microscopy, to N.S. Egorova and E.A. Sukhacheva (M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry, Moscow) for oligopeptide synthesis and raising polyclonal antiserum, to Y.S. Skoblov (V.A. Engelgardt Institute of Molecular Biology, Moscow) for [32P]NAD+ synthesis, to S. Smith (Skirball Institute of Biomolecular Medicine, New York) and T. de Lange (The Rockefeller University, New York) for construct TT20 (with the full-length tankyrase 1 cDNA), and to V.Y. Polyakov (A.N. Belozersky Institute, Moscow State University) for expert evaluation of the microscopical data and valuable discussions.
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This study was supported by the Russian Foundation for Basic Research (grant no. 03-04-48835, principal investigator A.N. Kuimov)
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Sidorova, N., Zavalishina, L., Kurchashova, S. et al. Immunohistochemical detection of tankyrase 2 in human breast tumors and normal renal tissue. Cell Tissue Res 323, 137–145 (2006). https://doi.org/10.1007/s00441-005-0053-8
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DOI: https://doi.org/10.1007/s00441-005-0053-8