Centrosome loss results in an unstable genome and malignant prostate tumors

Mengdie Wang, Raymond B Nagle, Beatrice S. Knudsen, Anne E Cress, Gregory C. Rogers

Research output: Contribution to journalArticle

Abstract

Localized, nonindolent prostate cancer (PCa) is characterized by large-scale genomic rearrangements, aneuploidy, chromothripsis, and other forms of chromosomal instability (CIN), yet how this occurs remains unclear. A well-established mechanism of CIN is the overproduction of centrosomes, which promotes tumorigenesis in various mouse models. Therefore, we developed a single-cell assay for quantifying centrosomes in human prostate tissue. Surprisingly, centrosome loss—which has not been described in human cancer—was associated with PCa progression. By chemically or genetically inducing centrosome loss in nontumorigenic prostate epithelial cells, mitotic errors ensued, producing aneuploid, and multinucleated cells. Strikingly, transient or chronic centrosome loss transformed prostate epithelial cells, which produced highly proliferative and poorly differentiated malignant tumors in mice. Our findings suggest that centrosome loss could create a cellular crisis with oncogenic potential in prostate epithelial cells.

Original languageEnglish (US)
JournalOncogene
DOIs
StateAccepted/In press - Jan 1 2019

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Centrosome
Prostate
Genome
Neoplasms
Chromosomal Instability
Epithelial Cells
Aneuploidy
Prostatic Neoplasms
Carcinogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Centrosome loss results in an unstable genome and malignant prostate tumors. / Wang, Mengdie; Nagle, Raymond B; Knudsen, Beatrice S.; Cress, Anne E; Rogers, Gregory C.

In: Oncogene, 01.01.2019.

Research output: Contribution to journalArticle

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