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Molecular and Cellular Biology, November 2008, p. 6870-6876, Vol. 28, No. 22
0270-7306/08/$08.00+0     doi:10.1128/MCB.00392-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Polo-Like Kinase 1 Is Essential for Early Embryonic Development and Tumor Suppression{triangledown} ,{ddagger}

Lin-Yu Lu,1,{dagger} Jamie L. Wood,2,3,{dagger} Katherine Minter-Dykhouse,4 Lin Ye,1 Thomas L. Saunders,5 Xiaochun Yu,1* and Junjie Chen2*

Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, BSRB 1520, Ann Arbor, Michigan 48109,1 Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520,2 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Rochester, Minnesota 55905,3 Department of Oncology, Mayo Clinic and Foundation, Rochester, Minnesota 55905,4 Transgenic Animal Model Core, University of Michigan, Ann Arbor, Michigan 481095

Received 7 March 2008/ Returned for modification 23 April 2008/ Accepted 6 September 2008

Polo-like kinases (Plks) are serine/threonine kinases that are highly conserved in organisms from yeasts to humans. Previous reports have shown that Plk1 is critical for all stages of mitosis and may play a role in DNA replication during S phase. While much work has focused on Plk1, little is known about the physiological function of Plk1 in vivo. To address this question, we generated Plk1 knockout mice. Plk1 homozygous null mice were embryonic lethal, and early Plk1–/– embryos failed to survive after the eight-cell stage. Immunocytochemistry studies revealed that Plk1-null embryos were arrested outside the mitotic phase, suggesting that Plk1 is important for proper cell cycle progression. It has been postulated that Plk1 is a potential oncogene, due to its overexpression in a variety of tumors and tumor cell lines. While the Plk1 heterozygotes were healthy at birth, the incidence of tumors in these animals was threefold greater than that in their wild-type counterparts, demonstrating that the loss of one Plk1 allele accelerates tumor formation. Collectively, our data support that Plk1 is important for early embryonic development and may function as a haploinsufficient tumor suppressor.

* Corresponding author. Mailing address for Xiaochun Yu: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, BSRB 1520, Ann Arbor, MI 48109. Phone: (734) 615-4945. Fax: (734) 647-7950. E-mail: xiayu{at}umich.edu. Mailing address for Junjie Chen: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520. Phone: (203) 785-3758. Fax: (203) 785-7482. E-mail: junjie.chen{at}yale.edu

{triangledown} Published ahead of print on 15 September 2008.

{ddagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{dagger} These authors contributed equally to this work.

Molecular and Cellular Biology, November 2008, p. 6870-6876, Vol. 28, No. 22
0270-7306/08/$08.00+0     doi:10.1128/MCB.00392-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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