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National Repository of Grey Literature

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Epigenetic regulation of gene expression in cancer progression and HIV-1 latency Kovářová, Denisa ; Hejnar, Jiří (advisor) ; Černá, Marie (referee) ; Rösel, Daniel (referee) Epigenetic mechanisms of transcriptional regulation and modulation of gene expression using RNA interference have become a powerfull tool for studying various cellular mechanisms, including tumor progression and viral latency. Advances in expression profiling have provided technology to detect candidate genes implicated in this complex process and bring other possibilities in the diagnosis and treatment of tumor diseases. In this work, I compare the gene expression profiles of v-src-transformed metastatic and nonmetastatic cells using microarray chip technology. Transcription factor homeodomain only protein X (HOPX) was identified as one of the differentially expressed genes. Activity of HOPX gene in several cancer types is usually controlled by promoter methylation. The role HOPX in metastatic formation was assessed by inoculation of cells with modulated expression of HOPX in a syngeneic chicken model system. After HOPX knockdown using shRNA, originally metastatic line showed decreased in vivo metastatic capacity. Further genomic analyses identified a cadre of genes affected by HOPX knockdown. These data demonstrate that HOPX is a metastasis-associated gene and that its knockdown decreases the metastatic activity of v-src-transformed cells through altered gene expression patterns. In the second... Detailed record

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