1. ¹Department of Gynecology and Obstetrics, School of Medicine, JW Goethe-University, Frankfurt, Germany
2. ²Department of Medical Microbiology, Immunology and Cell Biology & Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, USA
3. ³Department of Otorhinolaryngology, School of Medicine, JW Goethe-University, Frankfurt, Germany

Correspondence: Dr J Yuan or Dr K Strebhardt, Department of Gynecology and Obstetrics, School of Medicine, JW Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mails: yuan@em.uni-frankfurt.de or Strebhardt@em.uni-frankfurt.de

Received 6 July 2005; Revised 8 September 2005; Accepted 26 September 2005; Published online 7 November 2005.

Abstract

Cyclin B1 is the regulatory subunit of cyclin-dependent kinase 1 (Cdk1) and is critical for the initiation of mitosis. Accumulating data indicate that the deregulation of cyclin B1 is tightly linked to neoplastic transformation. To study the phenotype and the potential preclinical relevance, we generated HeLa cell lines stably transfected with the plasmids encompassing short hairpin RNA (shRNA) targeting cyclin B1. We demonstrate that the reduction of cyclin B1 caused inhibition of proliferation by arresting cells in G2 phase and by inducing apoptosis. Cells, entering mitosis, were impaired in chromosome condensation and alignment. Importantly, HeLa cells with reduced cyclin B1 were more susceptible to the treatment of small interfering RNA targeting Polo-like kinase 1 (Plk1) and to the administration of the chemotherapeutic agent taxol. Finally, HeLa cells with reduced cyclin B1 showed inhibited tumor growth in nude mice compared to that of control cells. In summary, our data indicate that cyclin B1 is an essential molecule for tumor cell survival and aggressive proliferation, suggesting that the downregulation of cyclin B1, especially in combination with other molecular targets, might become an interesting strategy for antitumor intervention.