Untersuchungen zum Stellenwert des Proliferationsantigens Ki-67 als diagnostischer und prognostischer Parameter bei Tumorerkrankungen Schlussbericht

The monoclonal antibody Ki-67 recognizes a nucleolar antigen, that is expressed predominantly in proliferating cells. The function of the protein is yet to be defined. Mab Ki-67 is being used in routine histopathology diagnosis to determine the proliferating fraction of certain tumor entities. The aim of this project was to characterize the antigen recognized by mab Ki-67 and to clone the corresponding cDNA. The understanding of Ki-67 antigen function was expected to reveal novel therapeutic, diagnostic, and prognostic modalities. Immunoprecipitations using mab Ki-67 revealed by SDS-PAGE analysis a nuclear protein of 120 kDa molecular weight. Screening a phage expression library many cDNA clones were obtained. Together they harbour an open reading frame of 2886 bp, that yet lacks a few N-terminal residues. The deduced aminoacid sequences reveal homologies to nuclear proteins lamin-A and -C. Future use of these cDNA clones may include: i) generation of recombinant Ki-67 for immunizations to obtain an antibody suitable for paraffin sections; ii) use of Ki-67 cDNA for the diagnosis of Ki-67 gene aberrations in tumor biopsies; and iii) use of anti-sense Ki-67 cDNA as an antiproliferative agent in cancer therapy. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(72,44) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman