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p100: A Novel Proliferation-Associated Nuclear Protein Specifically Restricted to Cell Cycle Phases S, G2 , and M
H.J. Heidebrecht,
F. Buck,
J. Steinmann,
R. Sprenger,
H.H. Wacker, and
R. Parwaresch
From the Department of Hematopathology and Lymph Node Registry, German Association of Pathologists at the University of Kiel, Kiel, Germany; the Department of Cell Biochemistry and Clinical Neurobiology, University of Hamburg, Hamburg, Germany; the Department of Immunology, University of Kiel, Kiel, Germany; and the Division of Molecular Immunology, Forschungsinstitut Borstel, Borstel, Germany.
By immunization with nuclear lysates of L428 cells, we raised a monoclonal mouse antibody, Ki-S2 (IgG1 ). In Western blots, this antibody recognizes a nuclear antigen with an apparent molecular mass of 100 kD, termed p100. Protein sequencing of p100 showed that this is a hitherto unknown protein. Immunohistochemical examination of cryostat and paraffin sections of nearly all human tissue types and neoplasms showed that p100 was exclusively expressed in the nuclei of a fraction of proliferating cells. Cell sorting and fluorescence-activated cell sorting analysis of stimulated peripheral blood mononuclear cells showed that p100 was exclusively expressed in proliferating cells from the transition G1/S until the end of cytokinesis. During mitosis, this protein is strictly associated with the spindle pole and with the mitotic spindle, whereas during S and G2 , p100 is diffusely distributed throughout the cell nucleus. Immediately after completion of cytokinesis, p100 was rapidly degraded. In L428 cells, p100 is phosphorylated at least during mitosis. It has a turnover time of about 1 hour. Studies on routinely processed paraffin sections of specimens of malignant lymphoma, benign and malignant nevocellular tumors, and breast cancer showed that in all cases less than 40% of the Ki-67-positive growth fraction expressed p100. Thus, p100 might prove to be a more reliable measure of cellular proliferation and one that is more closely correlated to cancer prognosis, beyond its general biologic relevance as a cell cycle protein.
Blood, Vol. 90 No. 1 (July 1), 1997:
pp. 226-233
© 1997 by The American Society of Hematology.
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