Characterisation of gene expression profiles of yeast cells expressing BRCA1 missense variants (Articolo in rivista)

Type
Label
  • Characterisation of gene expression profiles of yeast cells expressing BRCA1 missense variants (Articolo in rivista) (literal)
Anno
  • 2009-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.ejca.2009.04.025 (literal)
Alternative label
  • Di Cecco L; Melissari E; Mariotti V; Iofrida C; Galli A; Guidugli L; Lombardi G; Caligo MA; Iacopetti P; Pellegrini S; (2009)
    Characterisation of gene expression profiles of yeast cells expressing BRCA1 missense variants
    in European journal of cancer (1990)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Di Cecco L; Melissari E; Mariotti V; Iofrida C; Galli A; Guidugli L; Lombardi G; Caligo MA; Iacopetti P; Pellegrini S; (literal)
Pagina inizio
  • 2187 (literal)
Pagina fine
  • 2196 (literal)
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  • no (literal)
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  • http://www.sciencedirect.com/science/article/pii/S0959804909003293 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 45 (literal)
Rivista
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  • 7 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 12 (literal)
Note
  • ISI Web of Science (WOS) (literal)
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • a Department of Experimental Pathology, Medical Biotechnology, Epidemiology and Infectious Diseases, University of Pisa, via Roma 55, 56126 Pisa, Italy b Laboratory of Gene and Molecular Therapy, Institute of Clinical Physiology, CNR, 56124 Pisa, Italy c Section of Genetic Oncology Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa and Pisa University Hospital, 56126 Pisa, Italy (literal)
Titolo
  • Characterisation of gene expression profiles of yeast cells expressing BRCA1 missense variants (literal)
Abstract
  • no (literal)
  • Germline mutations in breast cancer susceptibility gene 1 (BRCA1) confer high risk of developing breast and ovarian cancers. Even though most BRCA1 cancer-predisposing mutations produce a non-functional truncated protein, 5-10% of them cause single amino acid substitutions. This second type of mutations represents a useful tool for examining BRCA1 molecular functions. Human BRCA1 inhibits cell proliferation in transformed Saccharomyces cerevisiae cells and this effect is abolished by disease-associated mutations in the BRCT domain. Moreover, BRCA1 mutations located both inside and outside the BRCT domain may induce an increase in the homologous recombination frequency in yeast cells. Here we present a microarray analysis of gene expression induced in yeast cells transformed with five BRCA1 missense variants, in comparison with gene expression induced by wildtype BRCA1. Data analysis was performed by grouping the BRCA1 variants into three sets: Recombination (R)-set (Y179C and S1164I), Recombination and Proliferation (RP)-set (I1766S and M1775R) and Proliferation (P)-set (A1789T), according to their effects on yeast cell phenotype. We found 470, 740 and 1136 differentially expressed genes in R-, P- and RP-set, respectively. Our results point to some molecular mechanisms critical for the control of cell proliferation and of genome integrity providing support to a possible pathogenic role of the analysed mutations. They also confirm that yeast, despite the absence of a BRCA1 homologue, represents a valid model system to examine BRCA1 molecular functions, as the molecular pathways activated by BRCA1 variants are conserved in humans. (literal)
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