Ki-67 expression is determined by the cell-cycle stage.

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Ki-67 expression is determined by the cell-cycle stage. Ki-67 expression is determined by the cell-cycle stage. A, Histogram of the number of MKI67 significantly correlated genes in colorectal tumors with respect to Spearman correlation values (all correlations adjusted P < 0.05). The upper right bar plots report the proportion and number of cell-cycle genes among genes above a given correlation coefficient. B, Ki-67 interactome obtained combining STRING database interactions and our own Ki-67 protein physical interactions for all genes with correlation > 0.5 in A. C, Comparison between MKI67 and other genes in TCGA breast cancer transcriptomic data showing that mitotic genes are strongly correlated with Ki-67 expression in all cancer subtypes. For a full heatmap of correlated genes with a cancer annotation see Supplementary Fig. S2D. D, Ki-67 levels in cycling cells are comparable between primary human fibroblasts (HDF) and cancer cells. Immuno-dot blot of Ki-67 and cyclin A2 proteins from asynchronous cell lysates from the indicated cell lines compared with total protein as loading control (LC) and β-tubulin. Controls include U2OS stably expressing shRNA control silencing or Ki-67 silencing vectors (where Ki-67 is absent but cyclin A2 remains) or HDF arrested by treatment with PD0332991 (both Ki-67 and cyclin A2 are absent). Bottom, quantitation of results by densitometry analysis. E, The ratio of Ki-67 to cyclin A2 mRNA is similar in all cell lines as quantified by qRT-PCR (experiment as in A). Michal Sobecki et al. Cancer Res 2017;77:2722-2734 ©2017 by American Association for Cancer Research