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Proliferating cell nuclear antigen (PCNA) expression in regenerating rat liver after partial hepatectomy

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Abstract

Proliferating cell nuclear antigen (PCNA) is a nuclear protein maximally elevated in the S phase of proliferating and transformed cells and is recognized by the monoclonal antibody PC-10 in paraffin tissue sections. The liver regenerative process after partial hepatectomy in rats was estimated with thein vivo incorporation of [3H]thymidine into liver DNA and the liver thymidine kinase activity. The expression of PCNA in rat liver after partial hepatectomy was performed by immunohistochemical staining with PC-10 in paraffin embedded tissues, at different time intervals up to 240 hr. Proliferating cell nuclear antigen expression, [3H]thymidine incorporation into DNA, and liver thymidine kinase activity exhibited marked oscillations during the liver regenerative process. A close relationship was demonstrated among DNA synthesis, thymidine kinase activity, and PC-10 score. Our results suggest that PC-10 monoclonal antibody may be used as a worthwhile proliferation index in the evaluation of the rate of liver regeneration in rats.

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References

  1. Michalopoulos GM: Liver regeneration: Molecular mechanisms of growth control. FASEB J 4:176–187, 1990

    Google Scholar 

  2. Kahn D, Stadler J, Terblanche J, Van Hoorn-Hickman R: Thymidine kinase: An inexpensive index of liver regeneration in a large animal model. Gastroenterology 79:907–911, 1980

    Google Scholar 

  3. Garcia RL, Coltera MD, Gown AM: Analysis of proliferative grade using antiPCNA/cyclin monoclonal antibodies in fixed embedded tissues. Comparison with flow cytometric analysis. Am J Pathol 154:223–235, 1988

    Google Scholar 

  4. Hall PA, Levison DA, Woods AL, Yu CC-W, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohn R, Dover R, Wassem NH, Lane DP: Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162:285–294, 1990

    Google Scholar 

  5. Miyachi K, Fritzler MJ, Tan EM: Autoantibody to a nuclear antigen in proliferating cells. J Immunol 121:2228–2234, 1978

    Google Scholar 

  6. Takasaki Y, Deng JS, Tan EM: A nuclear antigen associated with cell proliferation and blast transformation: Its distribution in synchronized cells. J Exp Med 154:1899–1909, 1981

    Google Scholar 

  7. Bravo R, Fey SJ, Bellatin J, Larsen PM, Arevalo J, Cellis JE: Identification of a nuclear and of a cytoplasmic polypeptide whose relative proportions are sensitive to changes in the rate of cell proliferation. Exp Cell Res 136:311–319, 1981

    Google Scholar 

  8. Celis JE, Bravo R, Larsen PM, Fey SJ: Cyclin: A nuclear protein whose level correlates directly with the proliferative state of normal as well as of transformed cells. Leuk Res 8:143–157, 1984

    Google Scholar 

  9. Mathews MB, Bernstein RM, Franza BR, Garrels JL: Identity of the proliferating nuclear antigen and cyclin. Nature 309:374–376, 1984

    Google Scholar 

  10. Celis JE, Celis A: Cell cycle dependent variations in the distribution of the nuclear protein cyclin/proliferating cell nuclear antigen in cultured cells: Subdivision of the S phase. Proc Natl Acad Sci USA 82:3262–3266, 1985

    Google Scholar 

  11. Higgins GM, Anderson RM: Experimental pathology of the liver. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12:186–201, 1931

    Google Scholar 

  12. Munro HN, Fleck A: Recent developments in the measurement of nucleic acids in biological materials. Analyst 91:78–88, 1966

    Google Scholar 

  13. Richards GM: Modifications of the diphenylamine reaction giving increased sensitivity and simplicity in the estimation of DNA. Anal Biochem 57:369–376, 1974

    Google Scholar 

  14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951

    Google Scholar 

  15. Sasaki K, Murakami T, Kawasaki M, Takahashi M: The cell cycle associated change of the Ki-67 reactive nuclear antigen expression. J Cell Physiol 133:579–584, 1987

    Google Scholar 

  16. Braylan RC, Diamond LW, Powell ML, Harty-Golda B: Percentage of cells in the S phase of the cell cycle in human lymphoma determined by flow cytometry: correlation with labelling index and survival. Cytometry 1:171–174, 1980

    Google Scholar 

  17. Seki S, Sakaguchi H, Kawakita N, Yanai A, Kim K, Mizoguchi Y, Kobayashi K: Identification and fine structure of proliferating hepatocytes in malignant and nonmalignant liver diseases by use of a monoclonal antibody against DNA polymerase alpha. Hum Pathol 21:1020–1030, 1990

    Google Scholar 

  18. Seki S, Sakaguchi H, Kawakita N, Yanai A, Kuroki T, Mizoguchi Y, Kobayashi K, Monna T: Detection of proliferating hepatocytes in patients with acute hepatic failure by mitotic figures and a monoclonal antibody against DNA polymerase alpha. Liver 11:118–126, 1991

    Google Scholar 

  19. Hall PA, Richards MA, Gregory WM, Ardane AJ, Lister TA, Stansfeld AG: The prognostic value of Ki-67 immunostaining in non-Hodgkin's lymphoma. J Pathol 154:223–235, 1988

    Google Scholar 

  20. Landberg G, Tan EM, Roos G: Flow cytometric multiparameter analysis of proliferating cell nuclear antigen/cyclin and Ki-67 antigen: A new view of the cell cycle. Exp Cell Res 187:111–118, 1990

    Google Scholar 

  21. Dubey DB, Staunton DE, Parekh AC, Schwarting GA, Antoniou D, Lazarus H, Yunis EJ: Unique proliferation-associated marker expressed on activated and transformed human cells defined by monoclonal antibody. J Natl Cancer Inst 78:203–212, 1987

    Google Scholar 

  22. Engstrom Y: Monoclonal antibodies against mammalian ribonucleotide reductase. Acta Chem Scand Ser B Org Chem Biochem 36:343–344, 1982

    Google Scholar 

  23. Lloyd RV, Wilson BS, Varani J, Gaur PK, Moline S, Makari JG: Immunocytochemical characterization of a monoclonal antibody that recognizes mitosing cells. Am J Pathol 121:275–283, 1985

    Google Scholar 

  24. Dippold WG, Gilbert J, DeLeo AB, Khoury G, Old LG: p53 transformation related protein: detection by monoclonal antibody in mouse and human cells. Proc Natl Acad Sci USA 8:1695–1699, 1981

    Google Scholar 

  25. Kawakita N, Seki S, Sakaguchi H, Yanai A, Kuroki T, Mizoguchi Y, Kobayashi K, Monna T: Analysis of proliferating hepatocytes using a monoclonal antibody against proliferating cell nuclear antigen/cyclin in embedded tissues from various liver diseases fixed in formaldehyde. Am J Pathol 140:513–520, 1992

    Google Scholar 

  26. Skopelitou AS, Korkolopoulou PA, Papanikolaou A, Christodoulou P, Thomas-Tsagli E, Pavlaki KJ: A comparative assessment of proliferating cell nuclear antigen (PCNA) immunostaining and of nucleolar organizer regions (NORs) staining in transitional cell carcinomas of the urinary bladder. Correlation with other conventional prognostic pathologic parameters. Eur Urol 22(3):235–245, 1992

    Google Scholar 

  27. Yu CC-W, Hall PA, Fletcher CDM, Camplejohn RS, Waseem NH, Lane DP, Levison DA: Haemangiopericytomas: The prognostic value of immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA). Histopathology 19:29–33, 1991

    Google Scholar 

  28. Benjamin DR, Gown AM: Aberrant cytoplasmic expression of proliferating cell nuclear antigen in Hodgkin's disease. Am J Sur Pathol 15:764–768, 1991

    Google Scholar 

  29. Bravo R, Macdonald-Bravo H: Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: Association with DNA replication sites. J Cell Biol 105:1549–1554, 1987

    Google Scholar 

  30. Bravo R, Celis JE: A search for differential polypeptide synthesis throughout the cell cycle of HeLa cells. J Cell Biol 84:795–802, 1980

    Google Scholar 

  31. Bravo R, Frank R, Blundell PA, Macdonald-Bravo H: Cyclin/PCNA is the auxiliary protein of DNA polymerase-δ. Nature 327:515–517, 1987

    Google Scholar 

  32. Woods AL, Hall PA, Shepherd NA, Hanby AM, Waseem NH, Lane DP, Levison DA: The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in primary gastrointestinal lymphomas and its relationship to histologic grade, S+G2+M phase fraction (flow cytometric analysis) and prognosis. Histopathology 18:21–27, 1991

    Google Scholar 

  33. Koukoulis G, Rayner A, Tan K-C, Williams R, Portmann B: Immunlocalization of regenerating cells after submassive liver necrosis using PCNA staining. J Pathol 166:359–368, 1992

    Google Scholar 

  34. Wolf HK, Michalopoulos GK: Hepatocyte regeneration in acute fulminant and nonfulminant hepatitis: a study of proliferating cell nuclear antigen expression. Hepatology 15:707–713, 1992

    Google Scholar 

  35. Ottavio L, Chang CD, Rizzo MG, Travalli S, Casadevall C, Baserga R: Importance of introns in the growth regulation of mRNA levels of the proliferating nuclear cell antigen. Mol Cell Biol 10:303–309, 1990

    Google Scholar 

  36. Shipman-Appasamy P, Cohen KS, Prystowsky MB: Interleukin-2-induced expression of proliferating cell nuclear antigen is regulated by transcriptional and post-transcriptional mechanisms. J Biol Chem 265:19180–19184, 1990

    Google Scholar 

  37. Bucher NL: Medical progress. Experimental aspects of hepatic regeneration. N Engl J Med 277:686–696, 1967

    Google Scholar 

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Theocharis, S.E., Skopelitou, A.S., Margeli, A.P. et al. Proliferating cell nuclear antigen (PCNA) expression in regenerating rat liver after partial hepatectomy. Digest Dis Sci 39, 245–252 (1994). https://doi.org/10.1007/BF02090193

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