Summary
Using a normal cell line derived from a human fetus, the disappearance and reappearance of the Ki-67-reactive antigen following modification of the cell cycle was observed and estimated immunohistologically. It was found that G1G0 arrest induced by serum deprivation resulted in loss of the antigen in 24 h in all but a few (usually less than 10%) of cells. Return to normal medium and resumption of growth was accompanied by reappearance in 30 h. When entry into S-phase was prevented by desferrioxamine, reappearance of the antigen still occurred but only lasted for about 24 h. Inhibition of protein synthesis with cycloheximide also caused fading and eventual loss of immunostaining. In view of the ease with which this antigen becomes undetectable with cessation of protein synthesis and interruption of the cell cycle, we agree with those who advise caution in the use of Ki-67 to measure growth fraction in changeable cell populations such as tumours.
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References
Baisch H, Gerdes J (1987) Simultaneous staining of exponentially growing versus plateau phase cells with the proliferation-associated antibody Ki-67 and propidium iodide: analysis by flow cytometry. Cell Tissue Kinet 20:387–391
Braun N, Papadopoulos T, Muller-Hermelink HK (1988) Cell cycle dependent distribution of the proliferation-associated Ki-67 antigen in human embryonic lung cells. Virchows Archiv [B] 56:25–33
Brooks RF (1977) Continuous protein synthesis is required to maintain the probability of entry into S phase. Cell 12:311–317
Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, Mac-Donald S, Pulford KAF, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229
van Dierendonck JH, Keijzer R, van de Velde CJH, Cornelisse CJ (1989) Nuclear distribution of the Ki-67 antigen during the cell cycle: comparison with growth fraction in human breast cancer cells. Cancer Res 49:2999–3006
Domagala W, Lasota J, Bartkowiak J, Weber K, Osborn M (1990) Vimentin is preferentially expressed in human breast carcinomas with low estrogen receptor and high Ki-67 growth fraction. Am JPathol 136:219–227
Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20
Gerdes J, Lemke H, Baisch H, Wacker H-H, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715
Gerdes J, van Baarlen J, Pileri S, Schwarting R, van Unnik JAM, Stein H (1987) Tumor cell growth fraction in Hodgkin’s disease. Am J Pathol 128:390–393
Grigioni WF, D’Errico A, Bacci F, Gaudio M, Mazziotti A, Goz-zetti G, Mancini AM (1989) Primary liver neoplasms: evaluation of proliferative index using MoAb Ki-67. J Pathol 158:23–29
Hall PA, Richards MA, Gregory WM, D’Ardenne AJ, Lister TA, Stansfeld AG (1988) The prognostic value of Ki-67 immunostaining in non-Hodgkin’s lymphoma. J Pathol 154:223–235
Hoffbrand AV, Ganeshaguru K, Hooton JWL, Tattersall MHN (1976) Effect of iron deficiency and desferrioxamine on DNA synthesis in human cells. Br J Haematol 33:517–526
Loke SL, Jaffe ES, Neckers LM (1987) Inhibition of in vitro DNA synthesis by the monoclonal antibody Ki67. Blood [Suppl 1] 70:157a
Sasaki K, Murakami T, Kawasaki M, Takahashi M (1987) The cell cycle associated change of the Ki-67 reactive nuclear antigen expression. J Cell Physiol 133:579–584
Sasaki K, Matsumura K, Tsuji T, Shinozaki F, Takahashi M (1988) Relationship between labeling indices of Ki-67 and BrdUrd in human malignant tumors. Cancer 62:989–993
Sasaki K, Matsumura K, Murakami T, Shinozaki F, Takahashi M (1989) Effects of serum deprivation on Ki-67-reactive antigen: expression in HeLa cells. Acta Pathol Jpn 39:638–642
Schonk DM, Kuijpers HJH, van Drunen E, van Dalen CH, Geurts van Kessel AHM, Verheijen R, Ramaekers FCS (1989) Assignment of the gene(s) involved in the expression of the proliferation-related Ki-67 antigen to human chromosome 10. Hum Genet 83:297–299
Verheijen R, Kuijpers HJH, Schlingemann RO, Boehmer ALM, van Driel R, Brakenhoff GJ, Ramaekers FCS (1989a) Ki-67 detects a nuclear matrix-associated proliferation-related antigen I. Intracellular localization during interphase. J Cell Sci 92:123–130
Verheijen R, Kuijpers HJH, van Driel R, Beck JLM, van Dierendonck JH, Brakenhoff GJ, Ramaekers FCS (1989b) Ki-67 detects a nuclear matrix-associated proliferation-related antigen II. Localization in mitotic cells and association with chromosomes. J Cell Sci 92:531–540
Wersto RP, Herz F, Gallagher RE, Koss LG (1988) Cell cycledependent reactivity with the monoclonal antibody Ki-67 during myeloid cell differentiation. Exp Cell Res 179:79–88
Zetterberg A, Larsson O (1985) Kinetic analysis of regulatory events in G1 leading to proliferation or quiescence of Swiss 3T3 cells. Proc Natl Acad Sci USA 82:5365–5369
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Littleton, R.J., Baker, G.M., Soomro, I.N. et al. Kinetic aspects of Ki-67 antigen expression in a normal cell line. Virchows Archiv B Cell Pathol 60, 15–19 (1991). https://doi.org/10.1007/BF02899522
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DOI: https://doi.org/10.1007/BF02899522