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The Proliferation Marker Thymidine Kinase 1 Level is High in Normal Kidney Tubule Cells Compared to other Normal and Malignant Renal Cells

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Pathology & Oncology Research

Abstract

The activity of the proliferation related enzyme thymidine kinase 1 (TK1) was reported to be 3-fold higher in extracts from normal kidney tissue as compare to renal carcinoma extracts [3]. To verify these unexpected results, determinations of the protein levels of TK1 in normal kidney and in samples from different types of renal cell carcinoma (RCC) were done with immunohistochemistry and Western blot analysis. Two anti-TK1 peptide antibodies reacting with different TK1 epitops were used. TK1 levels were high in tubule cells as compared to glomerulus cells and connective tissue cells, while an intermediary TK1 was observed in renal cell carcinoma (RCC) cells. Western blot analysis demonstrated high levels of TK1 in extract from normal kidney, and lower levels of TK1 in the RCC extracts. The specificity of TK1 staining was demonstrated in competition experiments with excess TK1 antigen. The high TK1 levels in normal kidney tubule cells suggest that they are in a form of activated G1-state. The relatively low TK1 level in RCC, representing TK1 expression in S-phase cells, is in accordance with the low overall proliferation rate of these tumors. These results suggest that cell cycle regulation of TK1 in normal tubule cells differ from that in other type of normal and malignant renal cells.

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References

  1. Rylova SN, Mirzaee S, Albertioni F, Eriksson S (2007) Expression of deoxynucleoside kinases and 5′-nucleotidases in mouse tissues: implications for mitochondrial toxicity. Biochem Pharmacol 74:169–75

    Article  CAS  PubMed  Google Scholar 

  2. Oudard S, Levalois C, Andrieu JM, Bougaran J, Validire P, Thiounn N, Poupon MF, Fourme E, Chevillard S (2002) Expression of genes involved in chemoresistance, proliferation and apoptosis in clinical samples of renal cell carcinoma and correlation with clinical outcome. Anticancer Res 22:121–128

    CAS  PubMed  Google Scholar 

  3. Mizutani Y, Wada H, Yoshida O, Fukushima M, Nakao M, Miki T (2003) Significance of thymidine kinase activity in renal cell carcinoma. J Urology 169:7 06–709

    CAS  Google Scholar 

  4. Mizutani Y, Wada H, Yoshida O, Fukushima M, Nonomura M, Nakao M, Miki T (2003) Significance of thymidylate synthase activity in renal cell carcinoma. Clin Cancer Res 9:1453–1460

    CAS  PubMed  Google Scholar 

  5. O’Neill KL, Zhang F, Li H, Fuja DG, Murray BK (2007) Thymidine kinase 1-a prognostic and diagnostic indicator in ALL and AML patients. Leukemia 21:560–563

    Article  PubMed  Google Scholar 

  6. He Q, Fornander T, Johansson H, Johansson U, Hu GZ, Rutqvist LE, Skog S (2006) Thymidine kinase 1 in serum predicts increased risk of distant or loco-regional recurrence following surgery in patients with early breast cancer. Anticancer Res 26:4753–4759

    CAS  PubMed  Google Scholar 

  7. Vogetseder A, Picard N, Gaspert A, Walch M, Kaissling N, Le Hir M (2007) The proliferation capacity of the renalproximal tubule involves the bulk of differentiated cells. Am J Physiol Cell Physiol doi:10.1152/ajpcell.00227

  8. Vogetseder A, Palan T, Bacic D, Kaissling B, Hir ML (2007) Proximal tubular epithelial cells are generated by division of differentiated cells in the healthy kidney. Am J Physiol Cell Physiol 292:C807–C813

    Article  CAS  PubMed  Google Scholar 

  9. Törnevik Y, Ullman B, Balzarini J, Wahren B, Eriksson S (1995) Cytotoxicity of 3′-azido-3′-deoxythymidine correlates with 3′-azidothymidine-5′-monophosphate (AZTMP) levels, whereas anti-human immunodeficiency virus (HIV) activity correlates with 3′-azidothymidine-5′-triphosphate (AZTTP) levels in cultured CEM T-lymphoblastoid cells. Biochem Pharmacol 49:829–37

    Article  PubMed  Google Scholar 

  10. He Q, Mao Y, Wu J, Decker C, Merza M, Wang N, Eriksson S, Castro J, Skog S (2004) Cytosolic thymidine kinase is a specific histopathologic tumour marker for breast carcinomas. Intern J Oncol 25:945–53

    CAS  Google Scholar 

  11. Gasparri F, Wang N, Skog S, Galvani A, Eriksson S (2009) Thymidine kinase 1 expression define an activated G1 state of the cell cycle as revealed with site specific antibodies and ArrayScan assays. Eur J Cell Biology 88:779–785

    Article  CAS  Google Scholar 

  12. Wu C, Yang R, Zhou J, Bao S, Zou L, Zhang P, Mao Y, Wu J, He Q (2003) Production and characterisation of a novel chicken IgY antibody raised against C-terminal peptide from human thymidine kinase 1. J Immunological Methods 277:157–169

    Article  CAS  Google Scholar 

  13. Ozono S, Miyao N, Igarashi T, Marumo K, Nakazawa H, Fukuda M, Tsushima T, Tokuda N, Kawamura J, Murai M (2004) and Collaboration Group of Japanese Society of Renal Cancer Tumor Doubling Time of Renal Cell Carcinoma Measured by CT. Jpn J Clin Oncol 34:82–85

    Article  PubMed  Google Scholar 

  14. Letocha H, Eklöv S, Gronowitz S, Norlén BJ, Nilsson S (1996) Deoxythymidine kinase in the staging of prostatic adenocarcinoma. Prostate 29:15–19

    Article  CAS  PubMed  Google Scholar 

  15. Wu JP, Mao YR, Hu LX, Wang N, Wu CJ, He Q, Skog S (2000) A new cell proliferating marker: Cytosolic thymidine kinase as compared to proliferating cell nuclear antigen in patients with colorectal carcinoma. Anticancer Res 20:4815–4820

    CAS  PubMed  Google Scholar 

  16. Mao Y, Wu JP, Skog S, Eriksson S, Zhao YW, Zhou J, He Q (2005) Expression of cell proliferating genes in patients with non-small cell lungcancer by immunohistochemistry and cDNA profiling. Oncology Report 13:837–46

    CAS  Google Scholar 

  17. Sherley JL, Kelly TJ (1988) Regulation of human thymidine kinase during the cell cycle. J Biol Chem 263:8350–8358

    CAS  PubMed  Google Scholar 

  18. Ke PY, Chang ZF (2004) Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome- CDH1-mediated pathway. Mol Cell Biol 24:514–526

    Article  CAS  PubMed  Google Scholar 

  19. Young AN, Amin MB, Moreno CS, Lim SD, Cohen C, Petros JA, Marshall FF, Neish A (2001) Expression profiling of renal epithelial neoplasms. A method for tumour classification and discovery of diagnostic molecular markers. Amer J Path 158:1639–1651

    CAS  PubMed  Google Scholar 

  20. Ke PY, Kuo YY, Hu CM, Chang ZF (2005) Control of dTTP pool size by anaphase promoting complex/cyclosome is essential for the maintenance of genetic stability. Genes Dev 19:1920–1933

    Article  CAS  PubMed  Google Scholar 

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Grants

This work was supported by grants from Karolinska Institute SS and EH, and by grants from the Swedish Research Council to SE.

Disclosure

J Zhou is the general manager of SSTK Inc., Shenzhen, China, the company that provided the TK1 kit. E He and S Skog are scientific consultants for SSTK Inc. P Luo, G Hu and J Zhang have no relation to any companies connected to this study. Staffan Eriksson is a stock owner and scientific officer of Arocell AB, Uppsala, Sweden, which produce one of the TK1 antibody used in this study. N Wang owns stocks in Arocell AB. This investigation was supported by TK1 kits by SSTK Inc., Shenzhen, China.

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Authors and Affiliations

  1. Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China

    Pengcheng Luo

  2. Department of Pathology, Karolinska University Hospital, 141 86, Stockholm, Sweden

    Naining Wang

  3. Department of Oncology, Karolinska University Hospital, Stockholm, 141 86, Sweden

    Ellen He & Sven Skog

  4. Department of Anatomy, Physiology & Biochemistry, Swedish University of Agricultural Science, Biomedical Center, PoBox 575, 751 23, Uppsala, Sweden

    Staffan Eriksson

  5. Sino-Swed Molecular Bio-Medicine Research Institute, Shenzhen, China

    Ellen He, Ji Zhou & Sven Skog

  6. Department of Central Laboratory, Jiangxi People´s Hospital, Nanchang, China

    Guozhu Hu

  7. Department of Urology, Renmin Hospital of Wuhan University, 238 Ziyang Road, Wuhan, Hubie Province, 430060, China

    Jie Zhang

Authors
  1. Pengcheng Luo
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  2. Naining Wang
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  3. Ellen He
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  4. Staffan Eriksson
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  5. Ji Zhou
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  6. Guozhu Hu
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  7. Jie Zhang
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  8. Sven Skog
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Corresponding authors

Correspondence to Staffan Eriksson or Jie Zhang.

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Luo, P., Wang, N., He, E. et al. The Proliferation Marker Thymidine Kinase 1 Level is High in Normal Kidney Tubule Cells Compared to other Normal and Malignant Renal Cells. Pathol. Oncol. Res. 16, 277–283 (2010). https://doi.org/10.1007/s12253-009-9222-5

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  • DOI: https://doi.org/10.1007/s12253-009-9222-5

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