Suppression of cell division by pKi-67 antisense-RNA and recombinant protein

Michael Duchrow*, Mirko Schmidt, Monika Zingler, Stefan Anemüller, Hans Peter Bruch, Rainer Broll

*Corresponding author for this work
16 Citations (Scopus)


The human antigen defined by the monoclonal antibody Ki-67 (pKi-67) is a human nuclear protein strongly associated with cell proliferation and found in all tissues studied. It is widely used as a marker of proliferating cells, yet its function is unknown. To investigate its function we suppressed pKi-67 expression by antisense RNA and overexpressed a partial structure of pKi-67 in HeLa cells. A BrdU-incorporation assay showed a significant decrease in DNA synthesis after antisense inhibition. Cell cycle analysis phase and indicated a higher proportion of cells in G1 a lower proportion of cells in S phase while the number of G2/M phase cells remained constant. Overexpression of a recombinant protein encoding three of the repetitive elements from exon 13 of pKi-67 had a similar effect to that obtained by antisense inhibition. The similarity of the effect of expressing 'Ki-67 repeats' and pKi-67 antisense RNA could be explained by a negative effect on the folding of the endogenous protein in the endoplasmatic reticulum. Furthermore excessive self-association of pKi-67 via the repeat structure could inhibit its nuclear transport, preventing it from getting to its presumptive site of action. We conclude that the Ki-67 protein has an important role in the regulation of the cell cycle, which is mediated in part by its repetitive elements.

Original languageEnglish
JournalCellular Physiology and Biochemistry
Issue number6
Pages (from-to)331-338
Number of pages8
Publication statusPublished - 2001


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