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Nuclear Distribution of the Ki-67 Antigen during the Cell Cycle: Comparison with Growth Fraction in Human Breast Cancer Cells¹

Departments of Surgery [J. H. v. D., R. K., C. J. H. v. d. V.] and Pathology [C. J. C.], University Hospital, P. O. Box 9600, 2300RC Leiden, The Netherlands

It has been claimed that the commercially available Ki-67 monoclonal antibody recognizes a nuclear antigen which is solely expressed in cycling cells. Therefore, at present, Ki-67 is increasingly used as a tool in evaluating growth fractions (GFs) of human tumors. Here we describe specific patterns in the expression and topological distribution of this antigen during the cell cycle in MCF-7 human breast cancer cells. Our results support earlier findings that the antigen belongs to a class of antigens associated with the structural organization of meta- and anaphase chromosomes, and proteins located near the cortical regions of prenucleolar bodies and nucleoli. Using 5'-bromodeoxyuridine-labeling technology, we show that the expression may be undetectably low at the onset of DNA replication.

Comparison of Ki-67 fractions (KFs) and GFs as estimated from continuous 5'-bromodeoxyuridine-labeling curves revealed that KF was invariably higher than GF: in exponentially growing cov362.c14 human ovary cancer cells, KF was only 3.5% higher than GF; in MCF-7 cells, 11.3 ± 4.6%. In MCF-7 cultures either growing under suboptimal conditions or treated with 10^-6 M tamoxifen, the difference was more pronounced. Furthermore, we evaluated the decrease of Ki-67-positive cells in nutritionally deprived and cell cycle-specific, drug-treated cultures. Since the results indicate that nonproliferating cells may retain the antigen for a considerable period of time, KF may not always be a reliable indicator of GF.

¹ This study was supported by the Netherlands Cancer Foundation, Grant IKW 87-12.

² To whom requests for reprints should be addressed.

Received 11/30/88. Accepted 2/27/89.

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