A Bioinformatic Analysis of Arginine-Sensitive Regulation of rat Hepatic Gene Expression. Rattus norvegicus

Goals of the Study: 1. Assess the scope of arginine-responsive hepatic gene expression using in vitro rat models. 2. Compare normal and tumorigenic cells 3. Identify potentially novel genes and pathways that may be subject to amino acid (arginine) regulation Background: We previously reported that mRNA levels of the tumor associated glycoprotein amino acid transporter TA1/LAT1/ CD98 light chain arginine increase in normal hepatic cells under low arginine conditions while levels are constitutive and high in hepatic tumor cells. This suggested LAT1 amino acid response was associated with the normal hepatic phenotype and lost in carcinogenesis and may impact cell growth and survival in the tumor microenvironment. We sought to investigate how many and what types of genes are responsive to a change in arginine levels over 18 hrs using an in vitro model system. Experimental design: Differential gene expression was determined by microarrays using samples from triplicates of normal and transformed cells subjected to 18 hour arginine-deprivation compared to controls Keywords = arginine Keywords = hepatocyte Keywords = cancer Keywords = rat Keywords = amino acid Keywords = gene regulation Keywords = microarray Keywords: repeat sample

研究目标：
1. 利用体外大鼠模型评估精氨酸(arginine)应答性肝脏基因表达的覆盖范围；
2. 对比正常细胞与致瘤细胞的基因表达特征；
3. 鉴定可能受氨基酸（精氨酸）调控的新型基因与信号通路。

研究背景：
本团队此前已报道，在低精氨酸条件下，正常肝细胞(hepatocyte)中肿瘤相关糖蛋白氨基酸(amino acid)转运蛋白TA1/LAT1/CD98轻链的mRNA水平显著升高，而肝肿瘤细胞中该转录本水平呈组成型高表达。上述结果提示，LAT1的氨基酸应答特性与正常肝细胞表型密切相关，且该特性在癌变过程中发生丢失，其可能对肿瘤微环境中的细胞生长与存活产生影响。本研究旨在通过体外模型系统，探究18小时内精氨酸水平变化所调控的基因数量与类型。

实验设计：
以正常细胞与转化细胞的三次生物学重复样本为材料，设置18小时精氨酸剥夺处理组与对照组，通过微阵列(microarray)技术检测两组间的差异基因表达情况。

关键词：
精氨酸；肝细胞；癌症(cancer)；大鼠(rat)；氨基酸；基因调控(gene regulation)；微阵列；重复样本(repeat sample)