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Pathway-specific
differences between tumor cell lines and normal and tumor tissue cells
Adam Ertel1,
Arun Verghese1, Stephen W Byers2, Michael
Ochs3 and Aydin Tozeren1*
1Center for Integrated
Bioinformatics, School of Biomedical Engineering, Science and Health
Systems, Bossone 714, Drexel University, 3143 Chestnut Street,
Philadelphia, PA 19104, USA. 2Lombardi Comprehensive Cancer
Center at Georgetown University, 3800 Reservoir Road, Washington DC
20057, USA. 3Division of Bioinformatics, Fox Chase Cancer
Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA -- Email:
Adam Ertel - ame28@drexel.edu; Arun Verghese - av73@drexel.edu;
Stephen W Byers - byerss@georgetown.edu; Michael Ochs - m_ochs@fccc.edu;
Aydin Tozeren* - aydin.tozeren@drexel.edu, * Corresponding author --
Received: 23 January 2006; Accepted: 2 November 2006; Published 2 November 2006.
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Background.
Cell lines are used in experimental investigation of cancer but
their capacity to represent tumor cells has yet to be
quantified.
The aim of the study was to identify significant alterations in
pathway usage in cell lines in comparison with normal and tumor
tissue.
Methods.
This study utilized a pathway-specific enrichment analysis of
publicly accessible microarray data and quantified the gene expression
differences between cell lines, tumor, and normal tissue cells for six
different tissue types.
KEGG pathways that are significantly different between cell lines and
tumors, cell lines and normal tissues and tumor and normal tissue were
identified through enrichment tests on gene lists obtained using
Significance Analysis of Microarrays (SAM).
Results.
Cellular pathways that were significantly upregulated in cell
lines compared to tumor cells and normal cells of the same tissue type
included ATP synthesis, cell communication, cell cycle, oxidative
phosphorylation, purine, pyrimidine and pyruvate metabolism, and
proteasome.
Results on metabolic pathways suggested an increase in the velocity
nucleotide metabolism and RNA production.
Pathways that were downregulated in cell lines compared to tumor and
normal tissue included cell communication, cell adhesion molecules (CAMs),
and ECM-receptor interaction.
Only a fraction of the significantly altered genes in tumor-to-normal
comparison had similar expressions in cancer cell lines and tumor
cells.
These genes were tissue-specific and were distributed sparsely among
multiple pathways.
Conclusion.
Significantly altered genes in tumors compared to normal tissue
were largely tissue specific.
Among these genes downregulation was a major trend.
In contrast, cell lines contained large sets of significantly
upregulated genes that were common to multiple tissue types.
Pathway upregulation in cell lines was most pronounced over metabolic
pathways including cell nucleotide metabolism and oxidative
phosphorylation. Signaling pathways involved in adhesion and
communication of cultured cancer cells were downregulated.
The three way pathways comparison presented in this study brings light
into the differences in the use of cellular pathways by tumor cells
and cancer cell lines.
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