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1型人类嗜T淋巴细胞病毒税对转化生长因子β1（TGF-β1）基因的反式激活：成人T细胞白血病中TGF-β1产生增加的潜在机制

Transactivation of the transforming growth factor beta 1 (TGF-beta 1) gene by human T lymphotropic virus type 1 tax: a potential mechanism for the increased production of TGF-beta 1 in adult T cell leukemia.

作者信息

Kim S J, Kehrl J H, Burton J, Tendler C L, Jeang K T, Danielpour D, Thevenin C, Kim K Y, Sporn M B, Roberts A B

机构信息

Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892.

出版信息

J Exp Med. 1990 Jul 1;172(1):121-9. doi: 10.1084/jem.172.1.121.

DOI:10.1084/jem.172.1.121
PMID:2358774
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2188182/
Abstract

We examined the effect of the human T lymphotropic virus type 1 (HTLV-I) Tax gene product on the human transforming growth factor beta 1 (TGF-beta 1) promoter. Transfection of deleted constructs of the TGF-beta 1 promoter revealed regions homologous with AP-1 binding sites that were required for Tax-induced transactivation of the TGF-beta 1 promoter. In addition, we examined the expression and secretion of TGF-beta in fresh leukemic cells isolated from patients with adult T cell leukemia (ATL) and in HTLV-1-infected T cell lines. We report that fresh leukemic cells from ATL patients constitutively produce high levels of TGF-beta 1 mRNA and secrete TGF-beta 1 but not TGF-beta 2 into the culture medium. In addition, long-term ATL cell lines expressed significant amounts of TGF-beta 1 mRNA as well as detectable levels of TGF-beta 1 protein. These results suggest a role for Tax in the upregulation of TGF-beta 1 in HTLV-I-infected cells.

摘要

我们研究了1型人类嗜T淋巴细胞病毒（HTLV-I）Tax基因产物对人类转化生长因子β1（TGF-β1）启动子的影响。对TGF-β1启动子缺失构建体的转染揭示了与AP-1结合位点同源的区域，这些区域是Tax诱导TGF-β1启动子反式激活所必需的。此外，我们检测了从成人T细胞白血病（ATL）患者分离的新鲜白血病细胞以及HTLV-1感染的T细胞系中TGF-β的表达和分泌情况。我们报告称，来自ATL患者的新鲜白血病细胞持续产生高水平的TGF-β1 mRNA，并分泌TGF-β1，但不向培养基中分泌TGF-β2。此外，长期培养的ATL细胞系表达大量的TGF-β1 mRNA以及可检测水平的TGF-β1蛋白。这些结果表明Tax在HTLV-I感染细胞中TGF-β1的上调中发挥作用。

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