Oncotarget

Research Papers:

Geminin overexpression induces mammary tumors via suppressing cytokinesis.

Zannel Blanchard, Rohit Malik, Nicole Mullins, Christine Maric, Hugh Luk, David Horio, Brenda Hernandez, Jeffrey Killeen and Wael M. ElShamy _

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Oncotarget. 2011; 2:1011-1027. https://doi.org/10.18632/oncotarget.363

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Abstract

Zannel Blanchard*, Rohit Malik*, Nicole Mullins, Christine Maric, Hugh Luk, David Horio, Brenda Hernandez, Jeffrey Killeen and Wael M. ElShamy

1Cancer Institute and Department of Biochemistry, University of Mississippi Medical Center, 2500 N. State St., G651-6, Jackson, MS 39216

*Denotes equal contribution

Received: November 28, 2011; Accepted: December 9, 2011; Published: December 17, 2011;

Keywords:Geminin overexpression induces mammary tumors

Correspondence:

Wael M. ElShamy, email:

Abstract

Aneuploidy plays an important role in the development of cancer. Here, we uncovered an oncogenic role for geminin in mitotic cells. In addition to chromatin, tyrosine phosphorylated geminin also localizes to centrosome, spindle, cleavage furrow and midbody during mitosis. Geminin binding to Aurora B prevents its binding to INCENP, and thus activation leading to lack of histone H3-(serine 10) phosphorylation, chromosome condensation failure, aborted cytokinesis and the formation of aneuploid, drug resistance cells. Geminin overexpressing human mammary epithelial cells form aneuploid, aggressive tumors in SCID mice. Geminin is overexpressed in more than half of all breast cancers analyzed. The current study reveals that geminin is a genuine oncogene that promotes cytokinesis failure and production of aneuploid, aggressive breast tumors when overexpressed and thus a worthy therapeutic target (oncotarget) for aggressive breast cancer.


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