DOI: 10.1002/hep.510260307. Ki-67 expression during rat liver regeneration after partial hepatectomy

Ki-67 expression during rat liver regeneration after partial hepatectomy

10.1002/hep.510260307

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Hepatology (276)

Abstract

Antibodies to the cell-cycle-associated Ki-67 protein have been widely used for more than a decade as markers of proliferative cells. The prototype antibody Ki-67 reacted only with snap-frozen human tissue, but a novel antibody, MIB-1, was able to detect the Ki-67 antigen in paraffin wax-embedded human tissue. The ability of MIB-5, a novel antibody reactive with the rat equivalent Ki-67 protein, to immunohistochemically detect cycling parenchymal and littoral cells in the regenerating rat liver is reported. Rats underwent a standard two-thirds partial hepatectomy (PH), and groups of three animals were killed at intervals for up to 192 hours after PH. DNA synthesis was monitored by flash labeling with bromodeoxyuridine, and the response was as expected with a significant upsurge in hepatocyte labeling at 16 to 17 hours after PH. On the other hand, MIB-5 labeled a relatively constant percentage of hepatocytes (4%-8%) during the first 16 hours after PH, before a large proportion became labeled, also at 17 hours. The temporal pattern of MIB-5 labeling was similar to that of bromodeoxyuridine labeling, although, as expected, MIB-5 indices were higher. Semiquantification of Ki-67 messenger RNA (mRNA) levels by reverse-transcription polymerase chain reaction showed modest (fourfold to fivefold) increases in abundance during the first 12 hours after PH, but then levels increased dramatically to be at least 15-fold those of intact liver at 36 hours after PH. Much higher than normal levels of Ki-67 mRNA persisted throughout the period of study and even at 96 hours after PH they were still ninefold greater than normal. This study has shown the usefulness of the MIB-5 antibody to monitor proliferation in the rat liver, and furthermore, the pattern of expression of both the mRNA and the protein suggest that the Ki-67 protein, with hitherto unknown function, is more abundant in DNA synthesis and mitosis than in the early or even very late first G1 phase.

Bibliography

Gerlach, C., Sakkab, D. Y., Scholzen, T., DaÎ²ler, R., Alison, M. R., & Gerdes, J. (1997). Ki-67 expression during rat liver regeneration after partial hepatectomy. Hepatology, 26(3), 573â578.

Authors 6

C Gerlach (first)
D Y Sakkab (additional)
T Scholzen (additional)
R Daβler (additional)
M R Alison (additional)
J Gerdes (additional)

References 25 Referenced 110

{'key': '10.1002/hep.510260307-BIB1|cit1', 'first-page': '873', 'volume-title': 'The biology of epithelial cell populations', 'volume': '2', 'author': 'Wright', 'year': '1984'} / The biology of epithelial cell populations by Wright (1984)
10.1126/science.7123245 / Science / Monoclonal antibody to 5-bromo and 5-iododeoxyuridine: a new reagent for detection of DNA replication by Gratzner (1982)
10.1177/096032719501401201 / Hum Exp Toxicol / Assessing cellular proliferation: what's worth measuring? by Alison (1995)
10.1002/ijc.2910310104 / Int J Cancer / Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation by Gerdes (1983)
10.4049/jimmunol.133.4.1710 / J Immunol / Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67 by Gerdes (1984)
10.1038/bjc.1987.54 / Br J Cancer / A comparison of three methods for the determination of the growth fraction in non-Hodgkin's lymphoma by Schrape (1987)
10.3109/10428199009050974 / Leuk Lymph / Comparison of the DNA content, bromodeoxyuridine incorporation, and Ki-67 antigen expression in human acute myeloid leukemia by Tazzari (1990)
10.1007/BF02889998 / Virchows Arch B / Müller-Hermelink HK. Cell cycle dependent distribution of the proliferation associated Ki-67 antigen in human embryonic lung cells by Braun (1988)
10.1111/j.1365-2184.1992.tb01435.x / Cell Prolif / Cell cycle dependent expression and stability of the nuclear protein detected by Ki-67 antibody in HL-60 cells by Bruno (1992)
10.1083/jcb.123.3.513 / J Cell Biol / The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins by Schlüter (1993)
{'key': '10.1002/hep.510260307-BIB11|cit11', 'first-page': '629', 'article-title': 'New Ki-67-equivalent murine monoclonal antibodies (MIB 1-3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 66 bp repetitive elements encoding for the Ki-67 epitope', 'volume': '68', 'author': 'Key', 'year': '1993', 'journal-title': 'Lab Invest'} / Lab Invest / New Ki-67-equivalent murine monoclonal antibodies (MIB 1-3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 66 bp repetitive elements encoding for the Ki-67 epitope by Key (1993)
Gerlach C Key G Kubuttat MHG Daßler R Baron B Gerdes J Eur J Cell Biol 1995 224A
{'key': '10.1002/hep.510260307-BIB13|cit13', 'first-page': '207A', 'article-title': 'Immunohistochemical assessment of the proliferation associated Ki-67 protein in rat embryos [Abstract]', 'volume': '28', 'author': 'Gerlach', 'year': '1995', 'journal-title': 'Cell Prolif'} / Cell Prolif / Immunohistochemical assessment of the proliferation associated Ki-67 protein in rat embryos [Abstract] by Gerlach (1995)
10.1002/path.1711680114 / J Pathol / Immunohistological detection of tumour growth fraction (Ki-67 antigen) in formalin-fixed and routinely processed tissues by Gerdes (1992)
10.1083/jcb.36.3.551 / J Cell Biol / The kinetics of cellular proliferation in regenerating liver by Fabrikant (1968)
10.1016/S0140-6736(87)90977-9 / Lancet / Prognostic relevance of the tumour-cell growth fraction in malignant non-Hodgkin's lymphomas [Letter] by Gerdes (1987)
{'key': '10.1002/hep.510260307-BIB17|cit17', 'first-page': '867', 'article-title': 'Immunobiochemical and molecular biological characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67', 'volume': '138', 'author': 'Gerdes', 'year': '1991', 'journal-title': 'Am J Pathol'} / Am J Pathol / Immunobiochemical and molecular biological characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67 by Gerdes (1991)
{'key': '10.1002/hep.510260307-BIB18|cit18', 'first-page': '1063', 'article-title': 'Tumour cell growth fractions in human malignant melanomas and the correlation to histopathological tumour grading', 'volume': '134', 'author': 'Kaudewitz', 'year': '1989', 'journal-title': 'Am J Pathol'} / Am J Pathol / Tumour cell growth fractions in human malignant melanomas and the correlation to histopathological tumour grading by Kaudewitz (1989)
10.1002/path.1711680202 / J Pathol / Ki-67 structure, function and new antibodies by Sawhney (1992)
10.1242/jcs.109.1.143 / J Cell Sci / The murine Ki-67 cell proliferation antigen accumulates in the nucleolar and heterochromatic regions of interphase cells and at the periphery of the mitotic chromosomes in a process essential for cell cycle progression by Starborg (1996)
10.1096/fasebj.10.5.8621056 / FASEB J / Posttranscriptional regulation of gene expression in liver regeneration: role of mRNA stability by Kren (1996)
10.3109/10428199409051655 / Leuk Lymph / Expression of Bcl-2 protein and Bcl-2 mRNA in normal and neoplastic lymphoid tissues by Akagi (1994)
10.1182/blood.V80.8.2044.2044 / Blood / Detection of Bcl-2 protein and Bcl-2 messenger RNA in normal and neoplastic lymphoid tissues by immunohistochemistry and in situ hybridization by Kondo (1992)
10.1016/S0168-8278(05)80224-7 / J Hepatol / Distribution and activity of glutamine synthase and carbomylphosphate synthase upon enlargement of the liver lobule by repeated hepatectomies by Wagenaar (1993)
10.1002/cyto.990120511 / Cytometry / Ki-67 labeling in postmitotic cells: different Ki-67 pathways within the 2c compartment by Du Manoir (1991)

Dates

Type	When
Created	21 years ago (July 27, 2004, 7:17 p.m.)
Deposited	5 months ago (March 24, 2025, 12:26 p.m.)
Indexed	3 days, 5 hours ago (Aug. 23, 2025, 9:54 p.m.)
Issued	27 years, 11 months ago (Sept. 1, 1997)
Published	27 years, 11 months ago (Sept. 1, 1997)
Published Print	27 years, 11 months ago (Sept. 1, 1997)

Funders 0

None

BibTeX

@article{Gerlach_1997, title={Ki-67 expression during rat liver regeneration after partial hepatectomy}, volume={26}, ISSN={0270-9139}, url={http://dx.doi.org/10.1002/hep.510260307}, DOI={10.1002/hep.510260307}, number={3}, journal={Hepatology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Gerlach, C and Sakkab, D Y and Scholzen, T and Daβler, R and Alison, M R and Gerdes, J}, year={1997}, month=sep, pages={573–578} }

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