Ki‐67 labeling in postmitotic cells defines different Ki‐67 pathways within the 2c compartment

Abstract

Simultaneous quantification of DNA and Ki‐67 proliferation‐associated antigen was performed using fluorescence image cytometry. In the MCF‐7 cell line, the Ki‐67 antigen content increases during the cell cycle, and its intranuclear distribution pattern varies. Quantitative evolution of Ki‐67 content as a function of nuclear area makes it possible to define several pathways followed by cells going through the 2c compartment. 1) In some cells, the amount of Ki‐67 antigen remains constant during G1 (Ki‐67 stable pathway), and a characteristic speckled pattern can be observed. 2) In the larger fraction of cells analyzed, there is a postmitotic decrease in the Ki‐67 (Ki‐67 decrease pathway) content. In this pathway, labeling is located in the nucleoplasm in small nuclei, is located in nucleoli in intermediate‐sized nuclei, and is absent from larger nuclei (G0). A progressive increase in Ki‐67 content (Ki‐67 increase pathway) was observed from intermediate‐sized nuclei to S phase nuclei. From these results, we hypothesize that the Ki‐67 stable pathway is the G1 phase of newly formed cells going directly to S phase in local optimal conditions of growth and that Ki‐67 decrease pathway and Ki‐67 increase pathway correspond to cells whose progression to S phase is regulated by extracellular factors. Copyright © 1991 Wiley‐Liss, Inc.