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Breast Cancer Research

, 7:P7.03 | Cite as

A model of the BRCA1/BRCA2 network

  • MA Pujana
  • J-DJ Han
  • LM Starita
  • M Tewari
  • JS Ahn
  • V Assmann
  • WM ElShamy
  • J-F Rual
  • R Gelman
  • K Gunsalus
  • R Greenberg
  • B Bohian
  • N Bertin
  • N Ayivi-Guedehoussou
  • KL Nathanson
  • BL Weber
  • DE Hill
  • DM Livingston
  • JD Parvin
  • M Vidal
Poster Presentation
  • 1.3k Downloads

Keywords

Breast Cancer Cellular Network Cancer Gene Chromosome Segregation Genetic Network 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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.

Copyright information

© BioMed Central 2005

Authors and Affiliations

  • MA Pujana
    • 1
  • J-DJ Han
    • 1
  • LM Starita
    • 2
  • M Tewari
    • 1
  • JS Ahn
    • 1
  • V Assmann
    • 3
  • WM ElShamy
    • 1
  • J-F Rual
    • 1
  • R Gelman
    • 4
  • K Gunsalus
    • 5
  • R Greenberg
    • 1
  • B Bohian
    • 1
  • N Bertin
    • 1
  • N Ayivi-Guedehoussou
    • 1
  • KL Nathanson
    • 6
  • BL Weber
    • 6
  • DE Hill
    • 1
  • DM Livingston
    • 1
  • JD Parvin
    • 2
  • M Vidal
    • 1
  1. 1.Department of Cancer BiologyDana-Farber Cancer InstituteBostonUSA
  2. 2.Department of PathologyHarvard Medical School, Brigham and Women's HospitalBostonUSA
  3. 3.Center for Experimental Medicine, Institute of Tumor BiologyUniversity Hospital Hamburg–EppendorfHamburgGermany
  4. 4.Department of Biostatistical ScienceDana-Farber Cancer InstituteBostonUSA
  5. 5.Department of BiologyNew York UniversityNew YorkUSA
  6. 6.Department of Hematology/OncologyUniversity of Pennsylvania Medical CenterPhiladelphiaUSA

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