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Epigenetic silencers and Notch collaborate to promote malignant tumours by Rb silencing

Author

Listed:
  • Dolors Ferres-Marco

    (Campus de San Juan)

  • Irene Gutierrez-Garcia

    (Campus de San Juan)

  • Diana M. Vallejo

    (Campus de San Juan)

  • Jorge Bolivar

    (Universidad de Cadiz, Poligono Rio San Pedro s/n)

  • Francisco J. Gutierrez-Aviño

    (Campus de San Juan)

  • Maria Dominguez

    (Campus de San Juan)

Abstract

Cancer is both a genetic and an epigenetic disease. Inactivation of tumour-suppressor genes by epigenetic changes is frequently observed in human cancers, particularly as a result of the modifications of histones and DNA methylation. It is therefore important to understand how these damaging changes might come about. By studying tumorigenesis in the Drosophila eye, here we identify two Polycomb group epigenetic silencers, Pipsqueak and Lola, that participate in this process. When coupled with overexpression of Delta, deregulation of the expression of Pipsqueak and Lola induces the formation of metastatic tumours. This phenotype depends on the histone-modifying enzymes Rpd3 (a histone deacetylase), Su(var)3-9 and E(z), as well as on the chromodomain protein Polycomb. Expression of the gene Retinoblastoma-family protein (Rbf ) is downregulated in these tumours and, indeed, this downregulation is associated with DNA hypermethylation. Together, these results establish a mechanism that links the Notch–Delta pathway, epigenetic silencing pathways and cell-cycle control in the process of tumorigenesis.

Suggested Citation

  • Dolors Ferres-Marco & Irene Gutierrez-Garcia & Diana M. Vallejo & Jorge Bolivar & Francisco J. Gutierrez-Aviño & Maria Dominguez, 2006. "Epigenetic silencers and Notch collaborate to promote malignant tumours by Rb silencing," Nature, Nature, vol. 439(7075), pages 430-436, January.
  • Handle: RePEc:nat:nature:v:439:y:2006:i:7075:d:10.1038_nature04376
    DOI: 10.1038/nature04376
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    Cited by:

    1. Gillie Benchorin & Richard Jangwon Cho & Maggie Jiaqi Li & Natalia Molotkova & Minoree Kohwi, 2024. "Dan forms condensates in neuroblasts and regulates nuclear architecture and progenitor competence in vivo," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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