Cyclin E expression and proliferation in breast cancer

Cyclin E is a part of the cell cycle machinery and aberrantly expressed in several malignancies including breast cancer. Since cyclin E is cell cycle specifically expressed, we wanted to examine the relation between prolifera tion and expression of cyclin E with special attention to tumours with over expression of the protein. Seventy-four breast tumours were analysed for th e expression of cyclin E by immunohistochemistry and Western blotting and r elated to the growth fraction determined by Ki-67. Significant correlations were obtained between the growth fraction, the percentage of cyclin E posi tive cells, the intensity of cyclin E and total amount of cyclin E determin ed by Western blotting. The majority of the tumours had less cyclin E than Ki-67 positive cells indicating a conserved cell cycle specific expression of the protein which further was supported by flow cytometric analysis of b reast cancer cell lines. The cell cycle specificity of cyclin E was found e ven in rumours with inactivated retinoblastoma protein (pRB) demonstrating the existence of a pRB independent regulation of cyclin E. A fraction of th e tumours had considerably elevated cyclin E levels that were not in relati on to the proliferative activity as observed for the other tumours. These t umours were in general highly proliferative and considered to overexpress c yclin E. Patients with rumours of high proliferative activity, high total c yclin E levels or disproportionally elevated cyclin E expressions in relati on to proliferation had significantly increased risk of death in breast can cer, whereas the intensity of the immunohistochemical cyclin E staining did not affect the survival.