Rabbit Anti-Human GLUT3 (a.a. 151-260) Polyclonal antibody [FITC]

Objective: The objectives of this study were to investigate the effects of maternal dietary energy types on the mRNA expressions of the placental nutrient transporter and intrauterine fetal growth and to examine whether altered intrauterine fetal growth could be associated with different gene expressions relating to fetal energy metabolism and DNA methylation. Methods: Seventy-two 3-mo-old rats were allocated to one of four groups: low fat/low fiber (L-L), low fat/high fiber, high fat/low fiber (H-L), or high fat/high fiber. Rats were fed the treatment diets 4 wk before mating and continued in pregnancy until sample collections were obtained on days 13.5 and 17.5 of pregnancy. Results: The fetal weight in the L-L group was significantly lower than that in the H-L group (P < 0.05). The placental nutrient transporter mRNA expressions of glucose transporter-3 (Slc2a3) and cationic amino acid transporter-1 (Slc7a1) in the L-L group with a decreased fetal weight were downregulated compared with that in the H-L group with an increased fetal weight. However, placental Slc2a1 and the system A amino acid transporter gene Slc38a4 mRNA expressions were adaptively upregulated by the L-L diet with a decreased fetal weight (P < 0.05). For the placental imprinted gene Igf-2 and H19 expressions, lower Igf-2 and higher H19 expressions were associated with the decreased fetal growth in the L-L group compared with the H-L group with an increased fetal weight. Different fetal growth was associated with different DNA methyltransferase-1 and methyltransferase-3a expressions (P > 0.05) and energy metabolism-related genes. Conclusion: Collectively, these results demonstrated that intrauterine fetal growth could be affected by different energy intake types through placenta nutrient transporter gene expressions, and different fetal growths were associated with altered fetal genes related to DNA methylation and energy metabolism. (C) 2012 Elsevier Inc. All rights reserved.

Objective Despite advances in the identification of epigenetic alterations in pancreatic cancer, their biological roles in the pathobiology of this dismal neoplasm remain elusive. Here, we aimed to characterise the functional significance of histone lysine methyltransferases (KMTs) and demethylases (KDMs) in pancreatic tumourigenesis. Design DNA methylation sequencing and gene expression microarrays were employed to investigate CpG methylation and expression patterns of KMTs and KDMs in pancreatic cancer tissues versus normal tissues. Gene expression was assessed in five cohorts of patients by reverse transcription quantitative-PCR. Molecular analysis and functional assays were conducted in genetically modified cell lines. Cellular metabolic rates were measured using an XF24-3 Analyzer, while quantitative evaluation of lipids was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Subcutaneous xenograft mouse models were used to evaluate pancreatic tumour growth in vivo. Results We define a new antitumorous function of the histone lysine (K)-specific methyltransferase 2D (KMT2D) in pancreatic cancer. KMT2D is transcriptionally repressed in human pancreatic tumours through DNA methylation. Clinically, lower levels of this methyltransferase associate with poor prognosis and significant weight alterations. RNAi-based genetic inactivation of KMT2D promotes tumour growth and results in loss of H3K4me3 mark. In addition, KMT2D inhibition increases aerobic glycolysis and alters the lipidomic profiles of pancreatic cancer cells. Further analysis of this phenomenon identified the glucose transporter SLC2A3 as a mediator of KMT2Dinduced changes in cellular, metabolic and proliferative rates. Conclusion Together our findings define a new tumour suppressor function of KMT2D through the regulation of glucose/fatty acid metabolism in pancreatic cancer.