TA1/LAT-1/CD98 light chain and system L activity, but not 4F2/CD98 heavy chain, respond to arginine availability in rat hepatic cells - Loss of response in tumor cells
TA1/LAT-1/CD98 light chain and system L activity, but not 4F2/CD98 heavy chain, respond to arginine availability in rat hepatic cells - Loss of response in tumor cells
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DOI：
10.1074/jbc.275.8.5347
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发表时间：
2000-02-25
影响因子：
4.8
通讯作者：
Thompson, NL
中科院分区：
文献类型：
--
作者：
Campbell, WA;Sah, DE;Thompson, NL
肿瘤相关基因-1/L氨基酸转运体-1(TA1/LAT-1)是新近发现的CD98型氨基酸转运体轻链和细胞活化标志物。我们之前对原代培养的大鼠肝细胞的研究表明，TA1 RNA水平对中等氨基酸浓度做出反应，这表明适应性调节，与转化细胞相关的高水平TA1表达也表明在肿瘤进展中发挥作用。本研究利用一组特征良好的大鼠肝细胞系，研究了TA1/CD98的表达、适应性反应和相关氨基酸转运与肿瘤转化的关系。我们发现：1)精氨酸耗竭时TA1的表达增加，但不是谷氨酰胺；2)在谷氨酰转肽酶阳性的转化细胞和肿瘤细胞中，TA1对精氨酸的反应丧失；3)4F2/CD98重链对精氨酸水平没有明显的反应；4)L系统对精氨酸的氨基酸转运活性与TA1/LAT-1mRNA的变化有关，而与总免疫反应蛋白的变化无关。我们的结果表明，CD98轻链可能作为环境传感器，对氨基酸的可获得性做出反应，其调节是复杂的。我们假设，TA1表达的改变是肝癌发生的早期事件，使肿瘤细胞具有生长或生存优势，特别是在氨基酸供应有限的情况下。
Tumor associated gene-1/L amino acid transporter-1 (TA1/LAT-1) was recently identified as a light chain of the CD98 amino acid transporter and cellular activation marker. Our previous studies with primary rat hepatocyte cultures demonstrated that TA1 RNA levels were responsive to media amino acid concentrations, suggesting adaptive regulation, High level TA1 expression associated with transformed cells also suggested a role in tumor progression. The present study examined the relationship of TA1/CD98 expression, adaptive response, and associated amino acid transport to neoplastic transformation using a panel of well characterized rat hepatic cell lines. We found 1) increased expression of TA1 in response to amino acid depletion, specific for arginine but not glutamine; 2) loss of TA1 response to arginine in gamma-glutamyl transpeptidase-positive transformed and tumorigenic cells; 3) no appreciable response of 4F2/CD98 heavy chain to arginine levels; and 4) correlation of system L amino acid transport activity in response to arginine with changes in TA1/LAT-1 mRNA but not total immunoreacting protein. Our results suggest this CD98 Light chain may act as an environmental sensor, responding to amino acid availability and that its regulation is complex. We hypothesize that altered TA1 expression is an early event in hepatocarcinogenesis giving neoplastic cells a growth or survival advantage, particularly under conditions of limited amino acid availability.