The association between cell proliferation and apoptosis: studies using the cell cycle-associated proteins Ki67 and DNA polymerase alpha

The process of apoptosis is associated with the inappropriate expression of cell cycle regulatory proteins, which has led to the proposal that the apoptotic pathway represents an abortive attempt to pass through the cell proliferation cycle. To investigate this hypothesis, we examined the expression of two proliferation-associated antigens in apoptotic cells. Apoptotic bodies seen in a range of normal and pathological tissues are often positive for the Ki67 antigen, indicating that these cells were in the cell cycle during the period that they died. In contrast, spontaneous apoptosis of human polymorphonuclear leukocytes maintained in culture was not associated with the expression of either Ki67 or DNA polymerase a. In addition, apoptotic bodies in the pre-menstrual endometrium did not express the Ki67 antigen. These results indicate that, contrary to previous suggestions, apoptosis does not always depend on cell cycle entry. The use of antibodies to Ki67 should be valuable in defining the association of apoptosis with proliferation in a wide range of cells and tissues.