High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells

Jewel Daniel, Jonathan Coulter, Ju Hyung Woo, Kathleen Wilsbach, Edward Gabrielson

Research output: Contribution to journalArticle

Abstract

Most human cancers are aneuploid and have chromosomal instability, which contrasts to the inability of human cells to normally tolerate aneuploidy. Noting that aneuploidy in human breast cancer correlates with increased expression levels of the Mps1 checkpoint gene, we investigatedwhether these high levels of Mps1 contribute to the ability of breast cancer cells to tolerate this aneuploidy.Reducing Mps1 levels in cultured human breast cancer cells by RNAi resulted in aberrant mitoses, induction of apoptosis, and decreased ability of human breast cancer cells to grow as xenografts in nude mice. Remarkably, breast cancer cells that survive reductions in levels of Mps1 have relatively less aneuploidy, as measured by copies of specific chromosomes, compared with cells that have constitutively high levels of Mps1. Thus, high levels of Mps1 in breast cancer cells likely contribute to these cells tolerating aneuploidy.

Original languageEnglish (US)
Pages (from-to)5384-5389
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number13
DOIs
StatePublished - Mar 29 2011

Keywords

  • Genomic instability

ASJC Scopus subject areas

  • General

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