Cyclin E Expression and Proliferation in Breast Cancer

Abstract

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 proliferation and expression of cyclin E with special attention to tumours with overexpression of the protein. Seventy-four breast tumours were analysed for the expression of cyclin E by immunohistochemistry and Western blotting and related to the growth fraction determined by Ki-67. Significant correlations were obtained between the growth fraction, the percentage of cyclin E positive cells, the intensity of cyclin E and total amount of cyclin E determined 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 breast cancer cell lines. The cell cycle specificity of cyclin E was found even in tumours with inactivated retinoblastoma protein (pRB) demonstrating the existence of a pRB independent regulation of cyclin E. A fraction of the tumours had considerably elevated cyclin E levels that were not in relation to the proliferative activity as observed for the other tumours. These tumours were in general highly proliferative and considered to overexpress cyclin E. Patients with tumours of high proliferative activity, high total cyclin E levels or disproportionally elevated cyclin E expressions in relation to proliferation had significantly increased risk of death in breast cancer, whereas the intensity of the immunohistochemical cyclin E staining did not affect the survival.