Skip to main content
SpringerLink
Log in

Cell cycle dependent distribution of the proliferation-associated Ki-67 antigen in human embryonic lung cells

  • Published:
Virchows Archiv B

Summary

The cell cycle-dependent distribution of the proliferation-associated Ki-67 antigen has been evaluated immunocytochemically in L-132 human fetal lung cells. The cells were synchronized and cell cycle phases were determined: G1 = 6.7 h, S =5.4 h, G2 = 8.5 h and mitosis = 1.3 h. The Ki-67 patterns were strictly correlated with the cell cycle phases. In late G1-phase, Ki-67 antigen was present only in the perinucleolar region. In the S-phase, Ki-67 staining was found homogeneously in the karyoplasm and in the perinucleolar region. G2-phase cells contained a finely granular Ki-67 staining in the karyoplasm with Ki-67-positive specks and perinucleolar staining. In early mitotic cells (pro-and metaphase) an intense perichromosomal Ki-67 staining was observed in addition to a homogeneously stained karyoplasm in prophase, and cytoplasm in metaphase. During ana-and telophase the Ki-67 antigen disappeared rapidly. In resting cells there was no Ki-67 staining.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Beckstead JH (1985) Optimal antigen localization in human tissues using aldehyde fixated plasitc-embedded sections. J Histochem Cytochem 33:954–958

    PubMed  CAS  Google Scholar 

  • Bouteille M, Bouvier D, Seve AP (1983) Heterogeneity and teritorial organization of the nuclear matrix and related structures. Int Rev Cytol 83:135–182

    Article  PubMed  CAS  Google Scholar 

  • Bradbury EM, Matthews HR (1982) Chromatin structure, histone modifications and the cell cycle. In: Nicolini C (ed) Cell growth: NATO Advanced Study Institutes Series A. Life Sci, vol 38. Plenum Press, New York, pp 411–454

    Google Scholar 

  • Bravo R, Frank R, Blundell PA, McDonald-Bravo H (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase-δ. Nature 326:515–517

    Article  PubMed  CAS  Google Scholar 

  • Burger PC, Shibata T, Kleihues P (1986) The use of the monoclonal antibody Ki-67 in the identification of proliferating cells: application to surgical neuropathology. Am J Surg Pathol 10:611–617

    Article  PubMed  CAS  Google Scholar 

  • Busch H, Smetana K (1970) The nucleolus, vol 1. Academic Press, London

    Google Scholar 

  • Chaly N, Bladon T, Setterfield G, Little JE, Kaplan FG, Brown DL (1984) Changes in distribution of nuclear matrix antigens during mitotic cell cycle. J Cell Biol 99:661–671

    Article  PubMed  CAS  Google Scholar 

  • Clevenger CV, Epstein AL (1984) Identification of a nuclear protein component of interchromatin granules using a monoclonal antibody and immunogold electron microscopy. Exp Cell Res 151:194–207

    Article  PubMed  CAS  Google Scholar 

  • Cooper S (1982) The continuum model: application to G1-arrest and G0. In: Nicolini C (ed) Cell growth: NATO advanced study institutes series A, Life sci, vol 38, Plenum Press, New York, pp 315–336

    Google Scholar 

  • Daskal Y, Smetana K, Busch H (1980) Evidence from studies on segregated nucleoli that nucleolar silver staining proteins C23 and B23 are in the fibrillar component. Exp Cell Res 127:285–291

    Article  PubMed  CAS  Google Scholar 

  • Davis FM, Wegner R-D, Rao PN (1987) Monoclonal antibody with specificity to mitotic chromosomes of primates. Exp Cell Res 170:417–427

    Article  PubMed  CAS  Google Scholar 

  • Epifanova OI, Abuladze MK, Zosimovskaya AI (1975) Effects of low concentrations of actinomycin D on the initiation of DNA synthesis in rapidly proliferating and stimulated cell cultures. Exp Cell Res 92:23–30

    Article  PubMed  CAS  Google Scholar 

  • Escande M-L, Gas N, Stevens BJ (1985) Immunolocalization of the 100 k nucleolar protein in CHO cells. Biol Cell 53:99–110

    PubMed  CAS  Google Scholar 

  • Franke WW, Schmid E, Wellsteed J, Grund C, Gigi O, Geiger B (1983) Change of cytokeratin filament organization during the cell cycle: Selective masking of an immunologie determinant in interphase PtK2 cells. J Cell Biol 97:1255–1260

    Article  PubMed  CAS  Google Scholar 

  • Franklin WA, Bibbo M, Doria MI, Dytch HE, Toth J, De-Sombre E, Wied GL (1987) Quantitation of estrogen receptor content and Ki-67 staining in breast carcinoma by microticas image analysis system. Anal Quant Cytol Histol 9:279–285

    PubMed  CAS  Google Scholar 

  • Gallee MP, van Steenbrugge GJ, ten Kate FJ, Schroeder FH, van der Kwast TH (1987) Determination of the proliferative fraction of a transplantable, hormone-dependent, human prostatic carcinoma (PC-82) by monoclonal antibody Ki-67: potential application for hormone therapy monitoring. J Natl Cancer Inst 79:1333–1340

    PubMed  CAS  Google Scholar 

  • Gerdes J, Lemke H, Baische H, Wacker HH, Schwab U (1984) Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715

    PubMed  CAS  Google Scholar 

  • Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human antigen associated with cell proliferation. Int J Cancer 31:13–20

    Article  PubMed  CAS  Google Scholar 

  • Gerdes J, Stein H, Pileri S, Rivano MT, Gobbi M, Ralfkiaer E, Nielsen KM, Pallesen G, Bartels H, Palestro G, Delsol G (1987) Prognostic relevance of tumor-cell growth fraction in malignant non-Hodgkin’s lymphomas. Lancet 2:448–449

    Article  PubMed  CAS  Google Scholar 

  • Giangaspero F, Doglioni C, Rivano MT, Pileri S, Gerdes J, Stein H (1987) Growth fraction in human brain tumors defined by the monoclonal antibody Ki-67. Acta Neurop 74:179–182

    Article  CAS  Google Scholar 

  • Hancock R, Boulikas T (1982) Functional organization in the nucleus. Int Rev Cytol 79:165–214

    Article  PubMed  CAS  Google Scholar 

  • Hügle B, Hazan R, Scheer U, Franke WW (1985) Localization of ribosomal protein S1 in the granular component of the interphase nucleolus and its distribution during mitosis. J Cell Biol 100:873–886

    Article  PubMed  Google Scholar 

  • Kaul S, Pfeifer GP, Drahovsky D (1984) Preparation of monoclonal antibodies against DNA-cytosine-5′-methyltransferase from human-placenta. Eur J Cell Biol 34:330–335

    PubMed  CAS  Google Scholar 

  • Koepsel RR, Khan SA (1986) Static and initiator-enhanced bending of DNA at a replication origin. Science 233:1316–1318

    Article  PubMed  CAS  Google Scholar 

  • Koepsel RR, Murray RW, Khan SA (1986) Sequence-specific interaction between the replication initiator protein of the plasmid pT181 and its origin of the replication. Proc Natl Acad Sci USA 83:5484–5488

    Article  PubMed  CAS  Google Scholar 

  • Lalor PA, Mapp PI, Hall PA, Revell PA (1987) Proliferative activity of cells in the synovium as demonstrated by a monoclonal antibody, Ki-67. Rheumatol Int 7:183–186

    Article  PubMed  CAS  Google Scholar 

  • Lelle RJ, Heidenreich W, Stauch G, Wecke I, Gerdes J (1987) Determination of growth fractions in benign breast disease (BBD) with monoclonal antibody Ki-67. J Cancer Res Clin Oncol 113:73–77

    Article  PubMed  CAS  Google Scholar 

  • Lloyd R, Wilson BS, Vrani J, Gaur PK, Moline S, Makari J (1985) Immunocytochemical characterization of a monoclonal antibody that recognizes mitosing cells. Am J Pathol 121:275–283

    PubMed  CAS  Google Scholar 

  • Matsuhashi S, Watanabe T, Hori K (1987) An antigen expressed in proliferating cells at late G1-S phase. Exp Cell Res 170:351–362

    Article  PubMed  CAS  Google Scholar 

  • McGurrin JF, Doria MI Jr, Dawson PJ, Karrison T, Stein HO, Franklin WA (1987) Assessment of tumor cell kinetics by immunohistochemistry in carcinoma of breast. Cancer 59:1744–1750

    Article  PubMed  CAS  Google Scholar 

  • McKeon FD, Tuffanelli DL, Kobayashi S, Kirschner MW (1984) The redistribution of a conserved nuclear envelope protein during the cell cycle suggests a pathway for chromosome condensation. Cell 36:83–92

    Article  PubMed  CAS  Google Scholar 

  • Olson MOJ, Guetzow K, Busch H (1981) Localization of phosphoprotein C23 in nucleoli by immunological methods. Exp Cell Res 135:259–265

    Article  PubMed  CAS  Google Scholar 

  • Palutke M, Kakuruga D, Tabaczka P (1987) A flow cytometric method for measuring lymphocyte proliferation directly from tissue culture plates using Ki-67 and propidium iodide. J Immunol Methods 105:97–105

    Article  PubMed  CAS  Google Scholar 

  • Pastolero GC, Mori S (1987) Expression of proliferation-associated nuclear antigen in human malignancies. Jpn J Exp Med 57:193–198

    PubMed  CAS  Google Scholar 

  • Pileri S, Gerdes J, Rivano M, Tazzari PL, Magnani M, Gobbi M, Stein H (1987) Immunohistochemical determination of growth-fractions in human permanent cell lines and lymphoid tumors: a critical comparision of monoclonal antibodies OKT9 and Ki-67. Br J Haematol 65:271–276

    Article  PubMed  CAS  Google Scholar 

  • Prelich G, Kostura M, Marhak DR, Mathews MB, Stillman B (1987a) The cell cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. Nature 326:471–475

    Article  PubMed  CAS  Google Scholar 

  • Prelich G, Tan CK, Kostura M, Mathews MB, So AG, Downey KM, Stillman B (1987b) Functional identity of proliferating cell nuclear antigen and a DNA polymerase delta auxiliary protein. Nature 326:517–520

    Article  PubMed  CAS  Google Scholar 

  • Puck TT (1964) Studies of the life cycle of mammalian cells. Cold Spring Harbor 29:167–176

    CAS  Google Scholar 

  • Puck TT, Steffen J (1963) Life cycle analysis of mammalian cells. Biophysic J 3:379–397

    CAS  Google Scholar 

  • Ralfkiaer E, Stein H, Bosq J, Gatter KC, Ralfkiaer N, Wantzin GL, Mason DY (1986) Expression of a cell-cycle-associated nuclear antigen (Ki-67) in cutaneous lymphoid infiltrates. Am J Dermatopathol 8:37–43

    Article  PubMed  CAS  Google Scholar 

  • Rao P, Engelberg J (1966) Effects of temperature on the mitotic cycle of normal and synchronized mammalian cells. In: Cameron IL, Padilla GM (eds) Cell synchrony, vol 1. Academic Press, New York, pp 332–351

    Google Scholar 

  • Roggendorf W, Schuster T, Pfeifer J (1987) Proliferative potential of menigiomas determined with the monoclonal antibody Ki-67. Acta Neuropathol 73:361–364

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Schmidt-Zachmann MS, Hügle B, Scheer U, Franke WW (1984) Identification and localization of a novel nucleolar protein of high molecular weight by a monoclonal antibody. Exp Cell Res 153:327–346

    Article  PubMed  CAS  Google Scholar 

  • Schwarting R, Gerdes J, Niehus J, Jaeschke J, Stein H (1986) Determination of growth fraction in cell suspensions by flow cytometry using the monoclonal antibody Ki-67. J Immunol Methods 90:65–70

    Article  PubMed  CAS  Google Scholar 

  • Stein H, Gerdes J, Schwab U, Lemke H, Mason DY, Ziegler A, Schienle W, Diehl V (1982) Identification of Hodgkin and Sternberg-Reed cells as a unique cell type derived from a newly-detected small-cell poulation. Int J Cancer 30:445–459

    Article  PubMed  CAS  Google Scholar 

  • Taylor EW (1965) Control of DNA synthesis in mammalian cells in culture. Exp Cell Res 40:316–332

    Article  PubMed  CAS  Google Scholar 

  • Terasima T, Tolmach LJ (1963) Growth and nucleic acid synthesis in synchronously dividing populations of HeLa cells. Exp Cell Res 30:347–362

    Article  Google Scholar 

  • Turner BM, Franchi L (1987) Identification of protein antigens associated with the nuclear matrix and with clusters of interchromatin granules in both interphase and mitotic cells. J Cell Sci 87:269–282

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pathology, Julius-Maximilians Universität, Josef-Schneider-Straße 2, D-8700, Würzburg, Federal Republic of Germany

    Norbert Braun, Thomas Papadopoulos & Hans Konrad Müller-Hermelink

Authors
  1. Norbert Braun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Papadopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Braun, N., Papadopoulos, T. & Müller-Hermelink, H.K. Cell cycle dependent distribution of the proliferation-associated Ki-67 antigen in human embryonic lung cells. Virchows Archiv B Cell Pathol 56, 25–33 (1988). https://doi.org/10.1007/BF02889998

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02889998

Key words

Search

Navigation