The Mre11 Complex Suppresses Oncogene-Driven Breast Tumorigenesis and Metastasis Journal Article


Authors: Gupta, G. P.; Vanness, K.; Barlas, A.; Manova-Todorova, K. O.; Wen, Y. H.; Petrini, J. H. J.
Article Title: The Mre11 Complex Suppresses Oncogene-Driven Breast Tumorigenesis and Metastasis
Abstract: The DNA damage response (DDR) is activated by oncogenic stress, but the mechanisms by which this occurs, and the particular DDR functions that constitute barriers to tumorigenesis, remain unclear. We established a mouse model of sporadic oncogene-driven breast tumorigenesis in a series of mutant mouse strains with specific DDR deficiencies to reveal a role for the Mre11 complex in the response to oncogene activation. We demonstrate that an Mre11-mediated DDR restrains mammary hyperplasia by effecting an oncogene-induced G2 arrest. Impairment of Mre11 complex functions promotes the progression of mammary hyperplasias into invasive and metastatic breast cancers, which are often associated with secondary inactivation of the Ink4a-Arf (CDKN2a) locus. These findings provide insight into the mechanism of DDR engagement by activated oncogenes and highlight genetic interactions between the DDR and Ink4a-Arf pathways in suppression of oncogene-driven tumorigenesis and metastasis. © 2013 Elsevier Inc.
Journal Title: Molecular Cell
Volume: 52
Issue: 3
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2013-11-07
Start Page: 353
End Page: 365
Language: English
DOI: 10.1016/j.molcel.2013.09.001
PROVIDER: scopus
PUBMED: 24120666
PMCID: PMC3902959
DOI/URL:
Notes: --- - "Export Date: 2 December 2013" - "CODEN: MOCEF" - "Source: Scopus"
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  1. John Petrini
    94 Petrini
  2. Hannah Yong Wen
    301 Wen
  3. Gaorav Gupta
    37 Gupta
  4. Afsar Barlas
    35 Barlas