Downregulation of cyclin B1 inhibits proliferation of breast cancer cells

Introduction: Breast cancer is the most common malignancy among females worldwide and its incidence is increasing every year. Although improvements have been made in context of early diagnosis, surgical techniques, adjuvant hormone therapy, chemotherapy and radiotherapy, breast cancer is still a leading cause of cancer mortality. Growing knowledge of biological signalling pathways in breast cancer generates an increasing impact on clinical diagnosis and therapy. In spite of the well-established breast cancer genes, such as BRCA1, BRCA2, HER2 and p53, emerging studies indicate that uncontrolled high expression of cyclin B1, the regulatory subunit of mitosis initiator Cdk1, is closely involved in neoplastic transformation of breast cancer. Thus, the depletion of cyclin B1 could be an attractive strategy for breast cancer therapy. Methods: In the present work, we applied small interfering RNA (siRNAs) targeted to cyclin B1 and analysed their impact on the proliferation of various breast cancer cell lines. To address this question, determination of cell number, cell cycle analysis, Western blot, kinase assay in vitro, apoptosis assay and colony forming assay have been used. Results: Cyclin B1 siRNAs reduced efficiently the protein level of cyclin B1 in MCF-7, BT-474, SK-BR-3 and MDA-MB-435 tumor cells and subsequently the activity of Cdc2/cyclin B1. Proliferation of the siRNAs-treated cells were strongly inhibited by arresting cells in G2/M phase as well as by inducing apoptosis in breast cancer cell lines. Furthermore, colony-forming ability was impaired after siRNAs treatment. In contrast, the siRNAs didn't affect the human mammary epithelial cells (HMECs). Conclusions: These data suggest that the downregulation of cyclin B1, in combination with other targets, could be a promising strategy for the future tailored therapy of breast cancer.

Eingereicht von: Yuan J

[e-mail]