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Proliferation marker pKi-67 occurs in different isoforms with various cellular effects
Mirko H H Schmidt1, Rainer Broll, Hans-Peter Bruch
1Surgical Research Laboratory, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Journal of Cellular Biochemistry
|March 30, 2004
Summary
The Ki-67 protein (pKi-67) has at least five splice variants, with different isoforms appearing at distinct stages of the cell cycle. This differential splicing impacts cell proliferation rates.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The Ki-67 antigen (pKi-67) is a widely used proliferation marker.
- Previous studies identified two pKi-67 splice variants differing by one exon.
Purpose of the Study:
- To identify and characterize novel splice variants of human pKi-67.
- To investigate the functional implications of pKi-67 alternative splicing in cell proliferation and the cell cycle.
Main Methods:
- Analysis of 93 human tissues, primarily brain tumors.
- Mitotic induction in human peripheral blood mononuclear cells.
- Transfection of mammalian cells with specific pKi-67 exons using a tetracycline-regulated expression system.
Main Results:
- Three new pKi-67 splice variants were identified, including two natural isoforms and one atypical version.
- Alternative splicing of the pKi-67 N-terminus is prevalent in tumor cell lines.
- The short pKi-67 isoform appears earlier in the cell cycle than the long isoform.
- Transfection with exon 7 (specific to the long isoform) reduced cell proliferation without altering the cell cycle.
Conclusions:
- The pKi-67 N-terminus undergoes differential splicing, generating at least five distinct isoforms.
- These isoforms exhibit distinct temporal expression patterns during the cell cycle.
- Differential splicing of pKi-67 isoforms influences cellular proliferation rates.