title: High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells.
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 investigated whether 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.
authors.affiliation: Department of Pathology and Johns Hopkins Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Jewel
authors.initials: J
authors.lastname: Daniel
authors.forename: Jonathan
authors.initials: J
authors.lastname: Coulter
authors.forename: Ju-Hyung
authors.initials: JH
authors.lastname: Woo
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wilsbach
authors.forename: Edward
authors.initials: E
authors.lastname: Gabrielson
mesh_terms: D000782:Aneuploidy; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases; D034622:RNA Interference; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human