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Open Access

A model of the BRCA1/BRCA2 network

  • MA Pujana1,
  • J-DJ Han1,
  • LM Starita2,
  • M Tewari1,
  • JS Ahn1,
  • V Assmann3,
  • WM ElShamy1,
  • J-F Rual1,
  • R Gelman4,
  • K Gunsalus5,
  • R Greenberg1,
  • B Bohian1,
  • N Bertin1,
  • N Ayivi-Guedehoussou1,
  • KL Nathanson6,
  • BL Weber6,
  • DE Hill1,
  • DM Livingston1,
  • JD Parvin2 and
  • M Vidal1
Breast Cancer Research20057(Suppl 2):P7.03

Published: 17 June 2005


Breast CancerCellular NetworkCancer GeneChromosome SegregationGenetic Network

Many genes/proteins have been involved in cellular transformation. However, a systems-level understanding of this pathological process is still absent. To address this question we developed a strategy to generate preliminary models of the networks around known cancer gene products. By examining functional genomic information as gene expression profiles, disease-associated genetic networks and systems-level integrated networks, we defined a 'breast cancer gene module' with predicted novel functional relationships to known breast cancer tumor suppressors. Genes within this module encoded for novel functional relationships with BRCA1 and BRCA2. Among the novel components identified we functionally characterized the hyaluronan-mediated motility receptor (HMMR, human Rhamm), which defines a BRCA1/BRCA2 protein network involved in the control of centrosome number and chromosome segregation. Biochemical data reveal that BRCA1/BRCA2 and HMMR form complexes, that HMMR is ubiquitinated by BRCA1/BARD1, and that BRCA1 and HMMR together regulate centrosome duplication in tissue culture cell lines derived from breast tissue. Our results indicate that similar strategies could help to build and complete other cancer-related cellular networks, and thus to understand how they are affected and/or contribute to cellular transformation.

Authors’ Affiliations

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, USA
Department of Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, USA
Center for Experimental Medicine, Institute of Tumor Biology, University Hospital Hamburg–Eppendorf, Hamburg, Germany
Department of Biostatistical Science, Dana-Farber Cancer Institute, Boston, USA
Department of Biology, New York University, New York, USA
Department of Hematology/Oncology, University of Pennsylvania Medical Center, Philadelphia, USA


© BioMed Central 2005