Browsing by Subject "microarray"

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Open Access
In silico analysis of mutant p53(R249S) oncogenicity in hepatocellular carcinoma
(2007) Ovezmuradov, Guvanchmurad
Oncogenic properties of mutant p53 proteins still stand as an ill-known subject, and the mechanism responsible for this phenomenon remains to be uncovered. This thesis aims to uncover the effect of p53 codon R249S ((AGG→AGT, arginine to serine) mutation on the development of hepatocellular carcinoma (HCC) through high throughput transcriptomics analysis using oligonucleotide arrays. We compared the expression profiles of HepG2 cells carrying wt and mutant p53(R249S). Microarray data analysis revealed a molecular signature consisting of 84 differentially regulated genes, showing that the expression of mutant p53(R249S) in HepG2 cells resulted in a distinct expression profile. Furthermore, mapping these significant differentiallyexpressed genes to the p53 interaction network revealed a putative interaction network representing functional outcomes of p53(R249S) expression in the context of diverse molecular interactions. Our results clearly demonstrated that several Hepatocyte Nuclear Factors (HNF1A, HNF4A and HNF6) could play an essential role in mediating mutant p53 oncogenic activity in HCC, as the key molecules of the gene network.
Open Access
Investigation of the effects of nicotine on the expression profile of SW620 colon adenocarcinoma cells using a functional genomics approach
(2009) Kaya, Onur
Colon cancer is the third most common form of cancer with approximately 655,000 deaths worldwide annually and the second principal cause of cancer-related death in the Western world. Studies focusing on genomic instability and cell culture in recent years have shown that there is a statistically significant link between tobacco smoking and colorectal cancer. Although nicotine is one of the most potent chemical in tobacco, it was not studied extensively in colorectal cancers. Nicotine works as an agonist of nicotinic acetylcholine receptors and modulates the intracellular calcium concentrations hence deregulating multiple signal transduction pathways (e.g., PI3K/AKT, MAPK, mTOR). It has been shown that nicotine accelerates cell proliferation while it increases cell migration, metastasis and angiogenesis, and inhibits apoptosis in lung and gastric cancers. The aim of this study was to give more insight into the association between nicotine and colon cancer by investigating the gene expression profiles of SW620 colon adenocarcinoma cells under 48h 1µM nicotine treatment at different serum levels to reflect molecular response to growth factor-induced and –depleted conditions (10% FBS or 0.1% FBS). We used multiple approaches including cell culture techniques, microarray technology, and gene-network analysis to assess the effects of nicotine on cell proliferation and transcriptome profile. Furthermore, the selected genes that are involved in cell cycle and apoptosis were used to confirm and evaluate the transcriptome analysis results with real time qRT-PCR and Western Blot techniques. In this project, our findings indicated that serum starvation of SW620 colon adenocarcinoma cell line resulted in decreased cell proliferation, which could be rescued by 1µM nicotine via deregulation of multiple pathways including cell cycle, apoptosis, Ca2+ signaling, and ribosomal protein expression. This study implicated that nicotine-, thus acetylcholine-mediated signaling may have an important role in tumor development and metastasis.