Chromosomal aneuploidy affects the global proteome equilibrium of colorectal cancer cells
2013 (English)In: Analytical Cellular Pathology, ISSN 2210-7185, Vol. 36, no 5-6, 149-161 p.Article in journal (Refereed) Published
BACKGROUND: Chromosomal aneuploidy has been identified as a prognostic factor in the majority of sporadic carcinomas. However, it is not known how chromosomal aneuploidy affects chromosome-specific protein expression in particular, and the cellular proteome equilibrium in general. OBJECTIVE: The aim was to detect chromosomal aneuploidy-associated expression changes in cell clones carrying trisomies found in colorectal cancer. METHODS: We used microcell-mediated chromosomal transfer to generate three artificial trisomic cell clones of the karyotypically stable, diploid, yet mismatch-deficient, colorectal cancer cell line DLD1 - each of them harboring one extra copy of either chromosome 3, 7 or 13. Protein expression differences were assessed by two-dimensional gel electrophoresis and mass spectrometry, compared to whole-genome gene expression data, and evaluated by PANTHER classification system and Ingenuity Pathway Analysis (IPA). RESULTS: In total, 79 differentially expressed proteins were identified between the trisomic clones and the parental cell line. Up-regulation of PCNA and HMGB I as well as down-regulation of IDH3A and PSMB3 were revealed as trisomy-associated alterations involved in regulating genome stability. CONCLUSIONS: These results show that trisomies affect the expression of genes and proteins that are not necessarily located on the trisomic chromosome, but reflect a pathway-related alteration of the cellular equilibrium.
Place, publisher, year, edition, pages
2013. Vol. 36, no 5-6, 149-161 p.
Aneuploidy, genomic instability, mass spectrometry, pathway analysis, two-dimensional gel-electrophoresis
Cell and Molecular Biology Cancer and Oncology
IdentifiersURN: urn:nbn:se:uu:diva-231143DOI: 10.3233/ACP-140088ISI: 000339705800004PubMedID: 24464829OAI: oai:DiVA.org:uu-231143DiVA: diva2:743543