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Geminin overexpression induces mammary tumors via suppressing cytokinesis.


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.

SUBMITTER: Blanchard Z 

PROVIDER: S-EPMC3282064 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Geminin overexpression induces mammary tumors via suppressing cytokinesis.

Blanchard Zannel Z   Malik Rohit R   Mullins Nicole N   Maric Christine C   Luk Hugh H   Horio David D   Hernandez Brenda B   Killeen Jeffrey J   Elshamy Wael M WM  

Oncotarget 20111201 12


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, dru  ...[more]

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