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National Repository of Grey Literature 2 records found  Search took 0.00 seconds. 
Characterization of tumor suppressor gene Hypermethylated in cancer 1 (Hic1) and its novel target genes in the intestinal epithelium and colorectal cancer
 Baloghová, Nikol ; Janečková, Lucie (advisor) ; Doubravská, Lenka (referee)
Colorectal cancer is one of the most common cancer types worldwide. Both genetic and epigenetic alterations play a critical role in its initiation and progression. One of the genes frequently epigenetically silenced or lost in many types of human cancer is tumor suppressor gene Hypermethylated in Cancer 1 (HIC1). It encodes for transcriptional repressor regulating its target genes directly or indirectly. Twelve genes whose expression is repressed by HIC1 have been identified to date. These genes encode for transcription factors, cell cycle and apoptosis regulators or proteins involved in angiogenesis as well as cell migration and invasiveness. Employing mouse embryonic fibroblasts upon Hic1-conditional knockout we have revealed six novel genes potentially repressed by Hic1 including Toll-like receptor 2 (Tlr2). Here we show that Tlr2 is one of the Hic1 target genes and that Hic1 inactivation in the intestine leads to increased Tlr2 production. Moreover, enhanced inflammatory response upon chemical-induced colitis as well as increased tumor formation in ApcMin mice was observed in Hic1-deficient mice. Expression profiling in human fibroblast upon HIC1 knockdown revealed increased expression of another potential target gene, transcription factor E2F7. Our study describes a new relationship between HIC1 and...
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Intestinal cancer and mouse models of the disease
 Baloghová, Nikol ; Janečková, Lucie (advisor) ; Gemperle, Jakub (referee)
Intestinal cancer is a serious and common disease. To understand the mechanisms of its development, it is important to know the structure of the intestinal epithelium, as well as the signalling pathways that maintain the homeostasis and regulate cell proliferation and differentiation. Development of the intestinal cancer is a multistep process in which many molecular events underlie initiation and progression of the disease. Transgenic mice produced by genetic engineering are essential tools in both research of the intestinal cancer initiation and progression and possible treatment strategies. The aim of this work is to describe the intestinal anatomy and the renewal of the intestinal epithelium including the role of multiple signalling pathways, to summarize the most common mutations conditioning human colorectal carcinoma development and to define the existing mouse models of the disease.
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