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.
Similar content being viewed by others
References
Michalopoulos GM: Liver regeneration: Molecular mechanisms of growth control. FASEB J 4:176–187, 1990
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
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
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
Miyachi K, Fritzler MJ, Tan EM: Autoantibody to a nuclear antigen in proliferating cells. J Immunol 121:2228–2234, 1978
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
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
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
Mathews MB, Bernstein RM, Franza BR, Garrels JL: Identity of the proliferating nuclear antigen and cyclin. Nature 309:374–376, 1984
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
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
Munro HN, Fleck A: Recent developments in the measurement of nucleic acids in biological materials. Analyst 91:78–88, 1966
Richards GM: Modifications of the diphenylamine reaction giving increased sensitivity and simplicity in the estimation of DNA. Anal Biochem 57:369–376, 1974
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951
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
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
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
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
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
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
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
Engstrom Y: Monoclonal antibodies against mammalian ribonucleotide reductase. Acta Chem Scand Ser B Org Chem Biochem 36:343–344, 1982
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
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
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
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
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
Benjamin DR, Gown AM: Aberrant cytoplasmic expression of proliferating cell nuclear antigen in Hodgkin's disease. Am J Sur Pathol 15:764–768, 1991
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
Bravo R, Celis JE: A search for differential polypeptide synthesis throughout the cell cycle of HeLa cells. J Cell Biol 84:795–802, 1980
Bravo R, Frank R, Blundell PA, Macdonald-Bravo H: Cyclin/PCNA is the auxiliary protein of DNA polymerase-δ. Nature 327:515–517, 1987
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
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
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
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
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
Bucher NL: Medical progress. Experimental aspects of hepatic regeneration. N Engl J Med 277:686–696, 1967
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02090193