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EXPRESSION & ROLE OF TA1 ONCOFETAL GENE--LIVER CANCER

表达

基本信息

批准号：
6628275
负责人：
NANCY L. THOMPSON
金额：
$ 24.17万
依托单位：
RHODE ISLAND HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-04-01 至 2005-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6628275
关键词：
aminoacid transport carcinogenesis gene expression genetic regulation human subject laboratory rat liver cells liver neoplasms oncogenes phenotype protein structure function tissue /cell culture

项目摘要

DESCRIPTION: (adapted from the investigator's abstract) TA1 was cloned as a cDNA with high level expression in rat hepatoma cell lines and fetal liver but not in normal adult liver. It's coding region is highly conserved, encoding a predicted 241 amino acid hydrophobic peptide with 6 or 7 transmembrane domains that is 94 percent identical to the human lymphocyte immediate early gene E16. Although homologs have recently been cloned in Xenopus, Schistosoma and C. elegans, its specific function remains unknown. TA1/E16 bears significant homology with yeast amino acid permeases and mammalian cationic amino acid transporters, strongly suggesting such a function. We have reported evaluated E16 expression in a variety of primary human cancer specimens relative to normal tissue, suggesting that upregulation of E16/TA1 expression is a common event in tumorigenesis. We have further demonstrated transient expression in acute rat liver injury and induced expression in normal hepatocytes in vitro following arginine depletion, findings consistent with the exploitation by tumor cells of a normal function in amino acid transport. The focus of this proposal is to examine the regulation and function of TA1/E16 in hepatic cells and its role in carcinogenesis. The hypothesis we propose to test is that while expression of TA1/E16 is tightly regulated in normal hepatic cells, consistutive high level expression contributes to the malignant phenotype, most likely by conferring a growth and/or survival advantage related to amino acid transport activity. In this proposal, we will use rat and human models in which to examine TA1 expression during hepatocarcinogenesis in vivo and compare its regulation in transformed and nontransformed hepatic cells in vitro. We will also determine the consequences of constitutive TA1 overexpression and blocked expression in heptatic cells on phenotype and the functional association of TA1 with CD98hc/4F2, a cell surface molecule implicated in integrin activation and amino acid transport. These studies will provide mechanistic insight into TA1 function and its role in liver carcinogenesis.

描述：（改编自研究者的摘要）TA1被克隆

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Transcriptional regulation of the LAT-1/CD98 light chain.

LAT-1/CD98 轻链的转录调控。

DOI：
10.1016/j.bbrc.2004.04.062
发表时间：
2004
期刊：
Biochemical and biophysical research communications
影响因子：
3.1
作者：
Padbury,JamesF;Diah,SriK;McGonnigal,Bethany;Miller,Carla;Fugere,Celine;Kuzniar,Magdalena;Thompson,NancyL
通讯作者：
Thompson,NancyL

Short-term arginine deprivation results in large-scale modulation of hepatic gene expression in both normal and tumor cells: microarray bioinformatic analysis.