Project description:Fatty acid synthase is a major enzyme involved in de novo lipogenesis, associated with energy homeostasis, lipid storage and signalling in normal liver cells. The effect of fatty acid synthase knockdown in normal liver cells (THLE 2) using siRNA mediated gene silencing were assesed for global gene deregulations. The deregulated metabolism, cell signalling and cell cycle pathway related gene expressions were analysed. Statistical significance values were also recorded. This expermental analysis clearly points to a important biochemical role for FASN in normal liver cell physiology. Total RNA was extracted from the THLE 2 cells transfected with FASN siRNA at 48h, along with its untransfected control cells. cDNA converted samples were run on microarray platform- Illumina HumanHT-12 V4.0 expression beadchip
Project description:Fatty acid synthase is a major enzyme involved in de novo lipogenesis and associated with tumor invasion and poor prognosis. The effect of fatty acid synthase knockdown in retinoblastoma cancer cells (WERI RB1) using siRNA mediated gene silencing were accessed for global gene deregulations. The analysis resulted in RB cancer cell death through deregulations of various cell signalling, metabolic, immunity, angiogenesis, apoptosis and cell cycle pathway related genes. Further validations were done using qRT-PCR and western analysis. Our results provide evidence that blockade in lipid metabolism inturn lead to RB cancer cell death through impaired cell signalling pathway.
Project description:A cDNA microarray was constructed from the expressed sequence tags (ESTs) of different developmental stages, and transcriptional profiles of the responses to PHS11A, a fatty acid synthase inhibitor, were determined. Keywords: treatment with fatty acid synthase inhibitor
Project description:The fatty acid synthase (FASN) is the major fat synthesizing enzyme. FASN is an indispensable enzyme because mice with genetic deletion of Fasn are not viable. Apart from its physiological function, previous studies indicated that FASN could also exert a pathophysiological role, in the heart, because patients with heart failure showed up-reguation of FASN. To investigate the in vivo function of FASN up-regulation in the heart, we generated mice with myocardium-specific expression of FASN under control of the alpha-MHC promoter. Two different founder lines were generated with high and low FASN over-expression. Microarray gene expression profiling of heart tissue was performed of heart tissue from transgenic mice with high and low FASN expression Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) Transgenic mice with high cardiac FASN expression, (ii) transgenic mice with low cardiac FASN expression, and (iii) B6 control mice.
Project description:Cigarette smoke has been demonstrated to stimulate the growth of existing bladder tumors by enhancing the survival and proliferation of cancer cells through the action of carcinogens present in smoke. Concurrently, Fatty Acid Synthase (FASN), a key enzyme in fatty acid synthesis crucial for lipid metabolism, exhibits dysregulation in various cancer types, often correlating with aggressive phenotypes. In this study, we reveal altered fatty acid metabolism and elevated FASN and fatty acid levels, specifically in current smokers with bladder cancer (BLCA). Notably, increased FASN levels under smoke exposure are attributed to epigenetic alterations affecting fatty acid metabolism. Cells exposed to cigarette smoke demonstrate a metabolic shift in utilizing glutamine as a carbon source and producing fatty acids. The genetic and pharmacological inhibition of FASN effectively reduces tumor growth in a CAM model exposed to smoke. FASN inhibitors like TVB 2640, currently in phase II clinical trialsclinical trials in various cancer types, may be effective for smokers with BLCA exhibiting high FASN levels. In general, FASN inhibition offers therapeutic promise for mitigating the impact of cigarette smoke on bladder cancer progression.
Project description:ATF6 is a key regulator of the unfolded protein response. Through use of zebrafish and cultured cells we demonstrate that ATF6 drives fatty liver disease by interaction with fatty acid synthase (FASN).
Project description:The fatty acid synthase (FASN) is the major fat synthesizing enzyme. FASN is an indispensable enzyme because mice with genetic deletion of Fasn are not viable. Apart from its physiological function, previous studies indicated that FASN could also exert a pathophysiological role, in the heart, because patients with heart failure showed up-reguation of FASN. To investigate the in vivo function of FASN up-regulation in the heart, we generated mice with myocardium-specific expression of FASN under control of the alpha-MHC promoter. Two different founder lines were generated with high and low FASN over-expression. Microarray gene expression profiling of heart tissue was performed of heart tissue from transgenic mice with high and low FASN expression
Project description:T. rubrum was treated with PH11B,a potent eucaryotic fatty acid synthase inhibtor. A cDNA microarray was constructed from the expressed sequence tags (ESTs) of different developmental stages, and transcriptional profiles of the responses to PH11B were determined. Some class-specific and mechanism-independent changes in gene expression were found. Keywords: fatty acid synthase inhibition
