Fig. 7.

Cyclin K expression positively correlates with tumorigenesis. a Ectopic cyclin K expression promoted anchorage-independent growth of NIH 3T3 cells in soft-agar assay. vec., vector. K-low, a cell line stably expressing cyclin K moderately above the endogenous level. K-high-1, K-high-2, two independent cell lines stably expressing high level of cyclin K. 1000 or 2500 cells of each cell line were seeded. Quantification was from four biological replicas. Data are means ± SEM (n = 4) (**p < 0.01; Student’s t-test). b Representative images of the ability of indicated cell lines to promote tumorigenesis in immunocompromised mice. K-high, representative image from both K-kigh-1 and 2 cell lines. More than ten mice were injected with individual cell line. Data are means ± SEM (n = 3) (**p < 0.01; Student’s t-test). c Pilot study of cyclin K expression in human invasive breast ductal carcinoma. Immunochemistry was carried out in paraffin-fixed specimens with a previously characterized anti-cyclin K antibody²². Lower panel, enlarged images of boxed areas in the upper panel. Scale bar, 100 μm for upper panel and 40 μm for lower panel. d Examination of cyclin K expression in our patient cohort containing early stage (upper panel, 70 patients), and late stage of breast carcinoma (lower panel, 68 patients). −, +, ++, +++, semi-quantification of cyclin K expression level by three trained pathologists at two different clinics (+++ denotes the highest expression of cyclin K). Scale bar, 100 μm. e Quantification of d. f Examination of CDK12, CDK13 and cyclin K expression in various human tumors. Expression data were extracted from COSMIC (Catalog of Somatic Mutations in Cancer, http://cancer.sanger.ac.uk/cosmic). g Kaplan–Meier plot of survival in ovarian and lung cancer patients with low or high expression of cyclin K. h Expression analyses of indicated genes in 66 cases of cyclin E1-overexpressing high-grade serous ovarian carcinoma. Expression data were extracted from COSMIC. Note that previous studies established that BRCA1 was required for continuous proliferation of cyclin E1-overexpressing cells⁴⁷