Article type: Research Article
Authors: Gemoll, Timo; ; | Habermann, Jens K.; ; | Becker, Susanne | Szymczak, Silke | Upender, Madhvi B. | Bruch, Hans-Peter | Hellman, Ulf | Ried, Thomas | Auer, Gert | Jörnvall, Hans | Roblick, Uwe J.;
Affiliations: Section for Translational Surgical Oncology & Biobanking, Department of Surgery, University of Lübeck, Lübeck, Germany | Karolinska Biomic Center, Karolinska Institutet, Stockholm, Sweden | Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden | Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA | Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany | Ludwig Institute for Cancer Research, Ltd. Uppsala, Uppsala, Sweden
Note: [] Corresponding author: Timo Gemoll, Ph.D., University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. Tel.: +49 451 5003917; Fax: +49 451 5002069; E-mail: [email protected] These authors contributed equally to this work.
Note: [] Corresponding author: Jens K. Habermann, M.D., Ph.D., University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. Tel.: +49 451 5003336; Fax: +49 451 5002069; E-mail: [email protected] These authors contributed equally to this work.
Abstract: 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 HMGB1 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.
Keywords: Aneuploidy, genomic instability, mass spectrometry, pathway analysis, two-dimensional gel-electrophoresis
DOI: 10.3233/ACP-140088
Journal: Analytical Cellular Pathology, vol. 36, no. 5-6, pp. 149-161, 2013
