Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth

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  • Additional Information
    • Affiliation:
      1 Mouse Biology Unit, European Molecular Biology Laboratory, Via Ramarini 32, 00015 Monterotondo, Italy
      2 Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
      3 Division of Molecular Thoracic Oncology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    • Note:
      Published: June 9, 2016
    • Abstract:
      Summary Chromosome instability (CIN) is associated with poor survival and therapeutic outcome in a number of malignancies. Despite this correlation, CIN can also lead to growth disadvantages. Here, we show that simultaneous overexpression of the mitotic checkpoint protein Mad2 with KrasG12D or Her2 in mammary glands of adult mice results in mitotic checkpoint overactivation and a delay in tumor onset. Time-lapse imaging of organotypic cultures and pathologic analysis prior to tumor establishment reveals error-prone mitosis, mitotic arrest, and cell death. Nonetheless, Mad2 expression persists and increases karyotype complexity in Kras tumors. Faced with the selective pressure of oncogene withdrawal, Mad2-positive tumors have a higher frequency of developing persistent subclones that avoid remission and continue to grow.
    • Abstract:
      @@@@Highlights •Mad2 overexpression leads to mitotic arrest, cell delamination, and cell death•High Mad2 levels delay oncogene-induced mammary tumorigenesis•Mad2 overexpression increases chromosome instability prior to and during tumor growth•Elevated Mad2 levels facilitate the development of oncogene-independent subclones
    • Abstract:
      @@@@Rowald et al. report that Mad2 overexpression in the mammary gland results in mitotic arrest, chromosome missegregation, and cell depletion, causing a delay in KrasG12D-driven mammary tumorigenesis. After oncogene silencing, however, Mad2-positive tumors show a frequent occurrence of persistent tumor subclones that do not regress.
    • ISSN:
      2211-1247
    • Accession Number:
      10.1016/j.celrep.2016.05.048
    • Accession Number:
      S2211124716306465
    • Copyright:
      © 2016 The Authors.
  • Citations
    • ABNT:
      ROWALD, K. et al. Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth. Cell Reports, [s. l.], v. 15, n. 12, p. 2679–2691, 2016. DOI 10.1016/j.celrep.2016.05.048. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edselp&AN=S2211124716306465. Acesso em: 7 ago. 2020.
    • AMA:
      Rowald K, Mantovan M, Passos J, et al. Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth. Cell Reports. 2016;15(12):2679-2691. doi:10.1016/j.celrep.2016.05.048
    • APA:
      Rowald, K., Mantovan, M., Passos, J., Buccitelli, C., Mardin, B. R., Korbel, J. O., Jechlinger, M., & Sotillo, R. (2016). Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth. Cell Reports, 15(12), 2679–2691. https://doi.org/10.1016/j.celrep.2016.05.048
    • Chicago/Turabian: Author-Date:
      Rowald, Konstantina, Martina Mantovan, Joana Passos, Christopher Buccitelli, Balca R. Mardin, Jan O. Korbel, Martin Jechlinger, and Rocio Sotillo. 2016. “Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth.” Cell Reports 15 (12): 2679–91. doi:10.1016/j.celrep.2016.05.048.
    • Harvard:
      Rowald, K. et al. (2016) ‘Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth’, Cell Reports, 15(12), pp. 2679–2691. doi: 10.1016/j.celrep.2016.05.048.
    • Harvard: Australian:
      Rowald, K, Mantovan, M, Passos, J, Buccitelli, C, Mardin, BR, Korbel, JO, Jechlinger, M & Sotillo, R 2016, ‘Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth’, Cell Reports, vol. 15, no. 12, pp. 2679–2691, viewed 7 August 2020, .
    • MLA:
      Rowald, Konstantina, et al. “Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth.” Cell Reports, vol. 15, no. 12, June 2016, pp. 2679–2691. EBSCOhost, doi:10.1016/j.celrep.2016.05.048.
    • Chicago/Turabian: Humanities:
      Rowald, Konstantina, Martina Mantovan, Joana Passos, Christopher Buccitelli, Balca R. Mardin, Jan O. Korbel, Martin Jechlinger, and Rocio Sotillo. “Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth.” Cell Reports 15, no. 12 (June 21, 2016): 2679–91. doi:10.1016/j.celrep.2016.05.048.
    • Vancouver/ICMJE:
      Rowald K, Mantovan M, Passos J, Buccitelli C, Mardin BR, Korbel JO, et al. Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth. Cell Reports [Internet]. 2016 Jun 21 [cited 2020 Aug 7];15(12):2679–91. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edselp&AN=S2211124716306465