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Molecular and Cellular Biology, March 2006, p. 2093-2108, Vol. 26, No. 6
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.6.2093-2108.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Normal Cells, but Not Cancer Cells, Survive Severe Plk1 Depletion

Xiaoqi Liu,1,2,{dagger}* Ming Lei,1,{dagger} and Raymond L. Erikson1

Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138,1 Department of Biochemistry and the Cancer Center, Purdue University, West Lafayette, Indiana 479072

Received 4 September 2005/ Returned for modification 18 October 2005/ Accepted 22 December 2005

We previously reported the phenotype of depletion of polo-like kinase 1 (Plk1) using RNA interference (RNAi) and showed that p53 is stabilized in Plk1-depleted cancer cells. In this study, we further analyzed the Plk1 depletion-induced phenotype in both cancer cells and primary cells. The vector-based RNAi approach was used to evaluate the role of the p53 pathway in Plk1 depletion-induced apoptosis in cancer cells with different p53 backgrounds. Although DNA damage and cell death can occur independently of p53, p53-deficient cancer cells were much more sensitive to Plk1 depletion than cancer cells with functional p53. Next, the lentivirus-based RNAi approach was used to generate a series of Plk1 hypomorphs. In HeLa cells, two weak hypomorphs showed only slight G2/M arrest, a medium hypomorph arrested with 4N DNA content, followed later by apoptosis, and a strong Plk1 hypomorph underwent serious mitotic catastrophe. In well-synchronized HeLa cells, a medium level of Plk1 depletion caused a 2-h delay of mitotic progression, and a high degree of Plk1 depletion significantly delayed mitotic entry and completely blocked cells at mitosis. In striking contrast, normal hTERT-RPE1 and MCF10A cells were much less sensitive to Plk1 depletion than HeLa cells; no apparent cell proliferation defect or cell cycle arrest was observed after Plk1 depletion in these cells. Therefore, these data further support suggestions that Plk1 may be a feasible cancer therapy target.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Ave., Cambridge, MA 02138. Phone: (617) 495-9686. Fax: (617) 495-0681. E-mail: liu13{at}fas.harvard.edu.

{dagger} X.L. and M.L. contributed equally to this study.

Molecular and Cellular Biology, March 2006, p. 2093-2108, Vol. 26, No. 6
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.6.2093-2108.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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