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Characterisation of gene expression profiles of yeast cells expressing BRCA1 missense variants
- Source :
- European Journal of Cancer. 45:2187-2196
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- 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 wild-type 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.
- Subjects :
- Genetics
Cancer Research
endocrine system diseases
Tumor suppressor gene
BRCA1 Protein
DNA repair
Microarray analysis techniques
Blotting, Western
Saccharomyces cerevisiae
Mutation, Missense
Biology
biology.organism_classification
BRCT domain
Germline mutation
Oncology
Gene expression
Humans
Female
skin and connective tissue diseases
Homologous recombination
Germ-Line Mutation
Cell Proliferation
Oligonucleotide Array Sequence Analysis
Subjects
Details
- ISSN :
- 09598049
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- European Journal of Cancer
- Accession number :
- edsair.doi.dedup.....988c04c19f8af8bffc9761e5470bb445