Ki67

Ki-67 is a large nuclear protein of approximately 395 kDa that is endogenously and differentially expressed at different levels at different phases of the cell cycle. Ki-67 is expressed in dividing cells for the entire duration of their mitotic process (Scholzen and Gerdes, 2000). Ki-67 protein undergoes phosphorylation and dephosphorylation during mitosis, it is susceptible to proteases and its structure implies that its expression is regulated by proteolytic pathways (Schluter et al., 1993).

Ki-67 protein also shares structural similarities with other proteins known to be involved in cell cycle regulation (Hofmann and Bucher, 1995). It has a very complex and specific localization patterns within the nucleus, one that changes during cell cycle. It is not expressed during the resting phase (Go) of the cell cycle, and its expression begins at the onset of G1.

This protein is present for the entire duration of the cell cycle, and disappears again once the cell exits the cycle and is in Go (Endl and Gerdes, 2000). Also it appears that the amount of Ki-67 protein present during cell cycle is highly regulated, presumably by precise synthesis and degradation systems, perhaps involving proteasome (protease complex shown to be involved in degradation of Ki-67 protein) (Brown and Gatter, 2002).

Similar to BrdU, Ki-67 can be detected with immunohistochemistry (figure 3). Unlike BrdU, Ki-67 is an endogenous marker that does not have any adverse effects on living cells. Although the function of Ki-67 is not known, it is a reliable marker of mitosis because it is expressed, albeit at different levels, during mitosis and its half-life is very short. Moreover, studies reported thus far, show that Ki-67 is expressed during mitosis in all mammalian species from rodents to humans (Scholzen and Gerdes, 2000; Endl and Gerdes, 2000).