Indoleamine 2,3-dioxygenase activity and L-tryptophan transport in human breast cancer cells
Indoleamine 2,3-dioxygenase activity and L-tryptophan transport in human breast cancer cells
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DOI：
10.1016/j.bbamem.2003.12.004
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发表时间：
2004-02-10
影响因子：
3.4
通讯作者：
Shennan, DB
中科院分区：
文献类型：
--
作者：
Travers, MT;Gow, IF;Shennan, DB
吲哚胺 2,3-双加氧酶的活性和表达以及 L-色氨酸转运已在培养的人乳腺癌细胞中进行了检查。 MDA-MB-231 但不 MCF-7 细胞表达吲哚胺 2,3-双加氧酶的 mRNA。 MDA-MB-231 细胞产生犬尿氨酸，作为酶活性的衡量标准，干扰素-γ（1000 单位/ml）显着刺激了 MDA-MB-231 细胞产生犬尿氨酸。因此，干扰素-γ增强了MDA-MB-231细胞对L-色氨酸的利用。 1-甲基-DL-色氨酸 (1 mM) 抑制 MBA-MB-231 细胞干扰素-γ 诱导的犬尿氨酸产生。当在存在干扰素-γ 的情况下培养时，MCF-7 细胞产生的犬尿氨酸保持在基础水平。 L-色氨酸通过不依赖 Na+ 的 BCH 敏感途径转运至 MDA-MB-231 细胞。 L 系统 (LAT1/CD98) 似乎是 L-色氨酸转运至这些细胞的唯一途径。 1-甲基-D,L-色氨酸反式刺激 L-色氨酸从 MDA-MB-231 细胞流出，因此似乎是 L 系统的转运底物。结果表明，L 系统在提供吲哚胺-2,3-双加氧酶及其主要底物 L-色氨酸方面发挥着重要作用，并提出了雌激素受体阴性乳腺癌细胞可能逃避免疫系统注意的机制。 (C) 2004 Elsevier B.V. 保留所有权利。
The activity and expression of indoleamine 2,3-dioxygenase together with L-tryptophan transport has been examined in cultured human breast cancer cells. MDA-MB-231 but not MCF-7 cells expressed mRNA for indoleamine 2,3-dioxygenase. Kynurenine production by MDA-MB-231 cells, which was taken as a measure of enzyme activity, was markedly stimulated by interferon-gamma (1000 units/ml). Accordingly, L-tryptophan utilization by MDA-MB-231 cells was enhanced by interferon-gamma. 1-Methyl-DL-tryptophan (1 mM) inhibited interferon-gamma induced kynurenine production by MBA-MB-231 cells. Kynurenine production by MCF-7 cells remained at basal levels when cultured in the presence of interferon-gamma. L-Tryptophan transport into MDA-MB-231 cells was via a Na+-independent, BCH-sensitive pathway. It appears that system L (LAT1/CD98) may be the only pathway for L-tryptophan transport into these cells. 1-Methyl-D,L-tryptophan trans-stimulated L-tryptophan efflux from MDA-MB-231 cells and thus appears to be a transported substrate of system L. The results suggest that system L plays an important role in providing indoleamine-2,3-dioxygenase with its main substrate, L-tryptophan, and suggest a mechanism by which estrogen receptor-negative breast cancer cells may evade the attention of the immune system. (C) 2004 Elsevier B.V. All rights reserved.