Cyclin E1 knockdown induces apoptosis in cancer cells

Objectives: Cyclin E1 is expressed during the late G1 phase of the cell cycle and mediates the initiation of DNA synthesis by activating cyclin-dependent kinases 2 (CDK2). Abnormally high levels of cyclin E1 expression have frequently been found in cancer cells. Here, we investigate the effect of cyclin E1 knockdown on cancer cells. Methods: RNA interference, expressed from a DNA-based retroviral vector, was used to knockdown cyclin E1 in adenocarcinoma (HeLa), breast (MDA-MB-31) and glioblastoma (U-373-MG) cell lines and an explant from one glioma patient (GB-LP-2). Results: We have obtained very efficient depletion of cyclin E1 protein (over 80%) and considerable apoptotic induction (50-70%) after 96 hours post-infection. The ability of U-373-MG cells to induce tumor growth in nude mice was also abolished after cyclin E1 knockdown. Discussion: Our results indicate that retrovirus carrying the DNA to be transcribed into a short hairpin RNA (shRNA) against cyclin E1 could be used as a therapeutic agent for cancer therapy.