| 1. |
- Gemoll, T, et al.
(författare)
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Chromosomal aneuploidy affects the global proteome equilibrium of colorectal cancer cells
- 2013
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Ingår i: Analytical cellular pathology (Amsterdam). - : Hindawi Limited. - 2210-7185 .- 2210-7177. ; 36:5-6, s. 149-161
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Gemoll, Timo, et al.
(författare)
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Chromosomal aneuploidy affects the global proteome equilibrium of colorectal cancer cells
- 2013
-
Ingår i: Analytical Cellular Pathology. - 2210-7177 .- 2210-7185. ; 36:5-6, s. 149-161
-
Tidskriftsartikel (refereegranskat)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 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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| 3. |
- Smirnova, IS, et al.
(författare)
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Hepatitis C virus core protein transforms murine fibroblasts by promoting genomic instability
- 2006
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Ingår i: Cellular oncology : the official journal of the International Society for Cellular Oncology. - : Hindawi Limited. - 1570-5870. ; 28:4, s. 177-190
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Tidskriftsartikel (refereegranskat)abstract
- The oncogenic potential of hepatitis C virus (HCV) core protein has been demonstrated, but the precise mechanism of cell transformation triggered by HCV core is still unclear. This study shows that constitutive expression of HCV core protein (core) in NIH 3T3 murine fibroblasts triggers malignant transformation. At the preneoplastic stage, clones that expressed HCV core constitutively demonstrated genomic instability seen as disruption of the mitotic spindle cell checkpoint leading to increased ploidy. Transformation was completed by the loss of DNA and resistance to apoptosis induced by serum starvation. Simultaneously, cells acquired a capacity for anchorage independent growth and absence of contact inhibition. Inoculation of these transformed cells into severe combined immune deficiency (SCID) mice led to formation of solid core-expressing tumors. Transformation and tumorigenicity of core-expressing cell lines coincided with a 5- to 10-fold repression of endogenous p53 transactivation. Thus, long-term HCV core expression alone is sufficient for complete transformation of immortal fibroblasts that can then induce tumors in a susceptible host. This data suggests that malignant transformation by HCV core may occur through primary stress, induction of genomic instability, and further HCV core-induced rescue of surviving mutated cells.
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