Chronic centrosome amplification without tumorigenesis

Benjamin Vitrea, Andrew J. Holland, Anita Kulukian, Ofer Shoshani, Maretoshi Hirai, Yin Wanga, Marcus Maldonado, Thomas Cho, Jihane Boubaker, Deborah A. Swing, Lino Tessarollo, Sylvia M. Evans, Elaine Fuchs, Don W. Cleveland

Research output: Contribution to journalArticlepeer-review

Abstract

Centrosomes are microtubule-organizing centers that facilitate bipolar mitotic spindle assembly and chromosome segregation. Recognizing that centrosome amplification is a common feature of aneuploid cancer cells, we tested whether supernumerary centrosomes are sufficient to drive tumor development. To do this, we constructed and analyzed mice in which centrosome amplification can be induced by a Cre-recombinase-mediated increase in expression of Polo-like kinase 4 (Plk4). Elevated Plk4 in mouse fibroblasts produced supernumerary centrosomes and enhanced the expected mitotic errors, but proliferation continued only after inactivation of the p53 tumor suppressor. Increasing Plk4 levels in mice with functional p53 produced centrosome amplification in liver and skin, but this did not promote spontaneous tumor development in these tissues or enhance the growth of chemically induced skin tumors. In the absence of p53, Plk4 overexpression generated widespread centrosome amplification, but did not drive additional tumors or affect development of the fatal thymic lymphomas that arise in animals lacking p53. We conclude that, independent of p53 status, supernumerary centrosomes are not sufficient to drive tumor formation.

Original languageEnglish (US)
Pages (from-to)E6321-E6330
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number46
DOIs
StatePublished - Nov 17 2015

Keywords

  • Centrosome amplification
  • P53
  • Plk4 kinase
  • Tumorigenesis

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Chronic centrosome amplification without tumorigenesis'. Together they form a unique fingerprint.

Cite this