Journal
ANALYTICAL CELLULAR PATHOLOGY
Volume 36, Issue 5-6, Pages 149-161Publisher
HINDAWI LTD
DOI: 10.1155/2013/249054
Keywords
Aneuploidy; genomic instability; mass spectrometry; pathway analysis; two-dimensional gel-electrophoresis
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Funding
- Swedish Cancer Society
- Cancer Society Stockholm
- Swedish Research Council
- German Cancer Aid Foundation (DKH e.V.) [108446]
- King Gustav V Jubilee Fund
- Wallenberg Consortium North
- Knut and Alice Wallenberg Foundation
- Werner and Clara Kreitz Foundation
- Ad Infinitum Foundation
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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.
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