Inhibition of BUB1 results in genomic instability and anchorage-independent growth of normal human fibroblasts

Antonio Musio, Cristina Montagna, Desirée Zambroni, Esterina Indino, Ottavia Barbieri, Lorenzo Citti, Anna Villa, Thomas Ried, Paolo Vezzoni

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


The relative contribution of aneuploidy and gene mutations to human tumorigenesis is not yet known. Studies in mice have demonstrated that even single point mutations in oncogenes and tumor suppressor genes can dramatically increase tumor frequency. However, models to evaluate the definitive role of aneuploidy and genomic instability are not yet available. Human fibroblast cells have long been used as a tool for investigating proliferation, senescence, immortalization, and tumorigenesis, all processes that are strongly interrelated. We have now used antisense and ribozyme-mediated temporary inhibition of BUB1 to study the consequences of mitotic checkpoint failure on the development of aneuploidy. The analysis of cell colonies selected by soft agar growth showed evidence of chromosome instability and delayed senescence, without being tumorigenic in nude mice. Our data suggest that chromosomal instability and aneuploidy are early changes that precede tumorigenicity in the multistep process leading to neoplastic transformation.

Original languageEnglish (US)
Pages (from-to)2855-2863
Number of pages9
JournalCancer research
Issue number11
StatePublished - Jun 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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