Chromosomal aneuploidy affects the global proteome equilibrium of colorectal cancer cells.
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.
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.
Timo
T
Gemoll
Section for Translational Surgical Oncology & Biobanking, Department of Surgery, University of Lübeck, Lübeck, Germany Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Jens K
JK
Habermann
Karolinska Biomic Center, Karolinska Institutet, Stockholm, Sweden.
Susanne
S
Becker
Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany.
Silke
S
Szymczak
Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Madhvi B
MB
Upender
Section for Translational Surgical Oncology & Biobanking, Department of Surgery, University of Lübeck, Lübeck, Germany.
Hans-Peter
HP
Bruch
Ludwig Institute for Cancer Research, Ltd. Uppsala, Uppsala, Sweden.
Ulf
U
Hellman
Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Thomas
T
Ried
Karolinska Biomic Center, Karolinska Institutet, Stockholm, Sweden.
Gert
G
Auer
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Hans
H
Jörnvall
Section for Translational Surgical Oncology & Biobanking, Department of Surgery, University of Lübeck, Lübeck, Germany Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Uwe J
UJ
Roblick
D000782:Aneuploidy; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D042822:Genomic Instability / Q000235:genetics / Q000502:physiology; D006801:Humans; D020543:Proteome / Q000378:metabolism*
D020543:Proteome
Aneuploidy; genomic instability; mass spectrometry; pathway analysis; two-dimensional gel-electrophoresis