| 1. |
- Jia, Min, et al.
(författare)
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Proteome profiling of immortalization-to-senescence transition of human breast epithelial cells identified MAP2K3 as a senescence-promoting protein which is downregulated in human breast cancer
- 2010
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Ingår i: PROTEOMICS - Clinical Applications. - : Wiley. - 1862-8346 .- 1862-8354. ; 4:10-11, s. 816-828
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Immortalization is one of the first changes in cells undergoing carcinogenic transformation. Proteome profiling of the immortalization-senescence transition is expected to provide insights into the molecular mechanisms of early tumorigenesis. Experimental design: 2-DE and MALDI-MS were used to identify proteins in primary human breast epithelial cells, relevant to the immortalization-senescence transition. Cell and molecular biology and immunohistochemistry were used to validate involvement of mitogen-activated protein kinase kinase 3 (MAP2K3) in the immortalization-senescence transition. Results: We identified 71 proteins whose expression changed upon induction of senescence. The identified proteins include regulators of cell growth, death, cell assembly and organization. Analysis of the network formed by the identified proteins suggested that the immortalization-to-senescence transition could affect regulators of the cell cycle, protein synthesis, transport, post-translational modifications, DNA recombination and repair, and lipid and amino acid metabolism. We observed that MAP2K3 was downregulated in immortal human breast epithelial cells and that upregulation of MAP2K3 expression promoted cell senescence. Decreased expression of MAP2K3 was observed in human breast infiltrating ductal carcinomas, as compared to non-cancerous human breast tissues. Conclusion and clinical relevance: We described a proteome profile of the immortalization-to-senescence transition for human breast epithelial cells, and identified MAP2K3 as a protein that promotes senescence in these cells.
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| 2. |
- Kannan, S., et al.
(författare)
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A LONG-TERM 10G-HYPERGRAVITY EXPOSURE PROMOTES CELL-CELL CONTACTS AND REDUCES ADHESIVENESS TO A SUBSTRATE, MIGRATION, AND INVASIVENESS OF MCF-7 HUMAN BREAST CANCER CELLS
- 2022
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Ingår i: EXPERIMENTAL ONCOLOGY. - : National Academy of Sciences of Ukraine (Co. LTD Ukrinformnauka) (Publications). - 1812-9269 .- 2312-8852. ; 44:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Background: G-force is a fundamental force controlling human cells. Cancer is one of the 4 major health challenges in the Space missions. Cancer in Space project evaluates the reaction of human cancer cells to the conditions of the space flights, including an exposure to high g-forces.Aim: Explore an impact of 10 g force on the oncogenic properties of human breast adenocarcinoma cells MCF-7. Materials andMethods: Cells were exposed to 10 g force for 10 days, as part of a 6-week simulation of conditions of a space flight. Then the cells were cultured for one week under normal culture conditions, before performing tests. Cell proliferation, cell viability, cell-cell contact inhibition, migration, and invasiveness were measured. Immunoblotting was used to evaluate expression of proteins.Results: Proliferation, cell-cell interaction and formation of 3D structures, migration, and invasiveness of cells exposed to 10 g were compared to parental cells cultured at 1 g condition. 10 g exposed cells showed a higher propensity for cell-cell contact inhibitions and lower for 3-dimensional growth in dense culture. This correlated with the decrease of proliferation in a dense culture as compared to the parental cells. The decrease of migration, adherence to a surface, and invasiveness was observed for cells subjected to the hypergravity, as compared to the parental MCF-7 cells. Enhanced expression of E-cadherin and phosphorylated pY576-FAK were observed in 10 g exposed cells but no impact on the expression of Erk, pErk, FAK and p53 was detected. Conclusion: The prolonged exposure of MCF-7 cells to 10 g force targets cell-cell and cell-substrate interactions.
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| 3. |
- Kwiecińska, Anna, et al.
(författare)
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Proteomic Profiling of Diffuse Large B-Cell Lymphomas
- 2018
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Ingår i: Pathobiology. - : S. Karger AG. - 1015-2008 .- 1423-0291. ; 85:4, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to identify differences in proteome profiles of diffuse large B-cell lymphoma (DLBCL) of nongerminal center (non-GC) versus GC type in the search for new markers and drug targets. Methods: Six DLBCL, with 3 repeats for each, were used for the initial study by proteomics: 3 non-GC and 3 GC DLBCL cases. For immunohistochemistry, tissue microarrays were made from 31 DLBCL samples: 16 non-GC de novo lymphomas and 15 GC cases (11 transformed from follicular lymphomas and 4 de novo GC lymphomas). Proteome profiling was performed by two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. Results: Ninety-one proteins were found differentially expressed in non-GC compared to GC type. The Cytoscape tool was used for systemic analysis of proteomics data, revealing 19 subnetworks representing functions affected in non-GC versus GC types of DLBCL. Conclusion: A validation study of 3 selected proteins (BiP/Grp78, Hsp90, and cyclin B2) showed the enhanced expression in non-GC DLBCL, supporting the proteomics data.
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| 4. |
- Sasaki, Takaaki, et al.
(författare)
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Elevated Intraocular Pressure, Optic Nerve Atrophy, and Impaired Retinal Development in ODAG Transgenic Mice
- 2009
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:1, s. 242-248
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. In an earlier study, a cDNA was cloned that showed abundant expression in the eye at postnatal day (P) 2 but was downregulated at P10; it was named ODAG (ocular development-associated gene). Its biological function was examined by generating and analyzing transgenic mice overexpressing ODAG (ODAG Tg) in the eye and by identifying ODAG-binding proteins. METHODS. Transgenic mice were generated by using the mouse Crx promoter. EGFP was designed to be coexpressed with transgenic ODAG, to identify transgene-expressing cells. Overexpression of ODAG was confirmed by Northern and Western blot analysis. IOP was measured with a microneedle technique. The eyes were macroscopically examined and histologically analyzed. EGFP expression was detected by confocal microscope. Proteins associated with ODAG were isolated by pull-down assay in conjugation with mass spectrometry. RESULTS. Macroscopically, ODAG Tg exhibited gradual protrusion of the eyeballs. The mean IOP of ODAG Tg was significantly higher than that of wild-type (WT) littermates. Histologic analysis exhibited optic nerve atrophy and impaired retinal development in the ODAG Tg eye. EGFP was expressed highly in the presumptive outer nuclear layer and weakly in the presumptive inner nuclear layer in the ODAG Tg retina. Rab6-GTPase-activating protein (Rab6-GAP) and its substrate, Rab6, were identified as ODAG-binding proteins. CONCLUSIONS. Deregulated expression of ODAG in the eye induces elevated intraocular pressure and optic nerve atrophy and impairs retinal development, possibly by interfering with the Rab6/Rab6-GAP-mediated signaling pathway. These results provide new insights into the mechanisms regulating ocular development, and ODAG Tg would be a novel animal model for human diseases caused by ocular hypertension.
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| 5. |
- Souchelnytskyi, Serhiy, et al.
(författare)
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COVID-19 engages clinical markers for the management of cancer and cancer-relevant regulators of cell proliferation, death, migration, and immune response
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Clinical reports show that the management of cancer patients infected with SARS-CoV-2 requires modifications. Understanding of cancer-relevant mechanisms engaged by the virus is essential for the evidence-based management of cancer. The network of SARS-CoV-2 regulatory mechanisms was used to study potential engagement of oncogenes, tumor suppressors, other regulators of tumorigenesis and clinical markers used in the management of cancer patients. Our network analysis confirms links between COVID-19 and tumorigenesis that were predicted in epidemiological reports. The COVID-19 network shows the involvement of tumorigenesis regulators and clinical markers. Regulators of cell proliferation, death, migration, and the immune system were retrieved. Examples are pathways initiated by EGF, VEGF, TGF beta and FGF. The SARS-CoV-2 network engages markers for diagnosis, prognosis and selection of treatment. Intersection with cancer diagnostic signatures supports a potential impact of the virus on tumorigenesis. Clinical observations show the diversity of symptoms correlating with biological processes and types of cells engaged by the virus, e.g. epithelial, endothelial, smooth muscle, glial and immune system cells. Our results describe an extensive engagement of cancer-relevant mechanisms and clinical markers by COVID-19. Engagement by the virus of clinical markers provides a rationale for clinical decisions based on these markers.
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