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Inhibition of BUB1 results in genetic instability and anchorance-indipendent growth of normal human fibroblasts (Articolo in rivista)

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Inhibition of BUB1 results in genetic instability and anchorance-indipendent growth of normal human fibroblasts (Articolo in rivista) (literal)

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Musio A., Montagna C., Zambroni D., Indino E., Barberi O., Citti L., Villa A., Ried T., Vezzoni P. (2003)
Inhibition of BUB1 results in genetic instability and anchorance-indipendent growth of normal human fibroblasts
in Cancer research (Chic. Ill.)
(literal)

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Musio A., Montagna C., Zambroni D., Indino E., Barberi O., Citti L., Villa A., Ried T., Vezzoni P. (literal)

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Rivista di riferimento internazionale nel settore della ricerca sul cancro con impact factor 8,318 (anno 2002). (literal)

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Originale modello che descrive i meccanismi precoci della tumorogenesi (literal)

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Musio A., Villa A., Vezzoni P.: Istituto di Tecnologie Biomediche del CNR di Milano, Citti L.: Istituto di Fisiologia Clinica del CNR di Pisa Montagna C., Ried T.: National Cancer Institute / NIH Bethesda, Maryland (U.S.) Zambroni D.: Centro Ricerche Parco Scientifico E. Menni, Brescia Indino E.: Istituto Zooprofilattico Sperimentale Lazio e Toscana, Dipartimento di Firenze Barbieri O.: Dipartimento di Oncologia Biologia e Genetica Università di Genova (literal)

Titolo

Inhibition of BUB1 results in genetic instability and anchorance-indipendent growth of normal human fibroblasts (literal)

Abstract

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 (literal)

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