Thioredoxin, a gene found overexpressed in human cancer, inhibits apoptosis in vitro and in vivo.
Thioredoxin, a gene found overexpressed in human cancer, inhibits apoptosis in vitro and in vivo.
复制标题
DOI：
--
复制
发表时间：
1997-11
期刊：
影响因子：
11.2
通讯作者：
Amanda F. Baker;Claire M. Payne;M. Briehl;Garth Powis
中科院分区：
文献类型：
--
作者：
Amanda F. Baker;Claire M. Payne;M. Briehl;Garth Powis
氧化还原蛋白硫氧还蛋白通过调节DNA合成和转录因子活性在控制癌细胞生长中起重要作用。硫氧还蛋白在许多人类原发性肿瘤中过表达，其表达在地塞米松诱导的小鼠WEHI 7.2胸腺瘤细胞凋亡过程中降低。我们研究了稳定转染人硫氧还蛋白cDNA的WEHI 7.2细胞在体外和体内进行细胞凋亡的能力，显示细胞质硫氧还蛋白水平增加。地塞米松，星形孢菌素，依托泊苷，毒胡萝卜素诱导的细胞凋亡的保护，但不是由N-乙酰鞘氨醇。当接种到严重的联合免疫缺陷小鼠中时，trx转染的细胞形成的肿瘤与野生型以及bcl-2转染的WEHI7.2细胞相比生长增加。与野生型细胞形成的肿瘤相比，trx-和bcl-2-转染的细胞肿瘤均表现出较少的自发性凋亡。与野生型和bcl-2转染的WEHI7.2细胞形成的肿瘤不同，trx转染的细胞肿瘤在用地塞米松处理后没有显示出生长抑制。这项研究表明，增加硫氧还蛋白在人类癌症中的表达可能会导致增加肿瘤的生长，通过抑制自发性细胞凋亡和降低肿瘤对药物诱导的细胞凋亡的敏感性。
The redox protein thioredoxin plays an important role in controlling cancer cell growth through regulation of DNA synthesis and transcription factor activity. Thioredoxin is overexpressed by a number of human primary cancers and its expression is decreased during dexamethasone-induced apoptosis of mouse WEHI7.2 thymoma cells. We examined the ability of WEHI7.2 cells stably transfected with human thioredoxin cDNA showing increased levels of cytoplasmic thioredoxin to undergo apoptosis in vitro and in vivo. The cells were protected from apoptosis induced by dexamethasone, staurosporine, etoposide, and thapsigargin, but not by N-acetyl-sphingosine. When inoculated into severe combined immunodeficient mice, the trx-transfected cells formed tumors that showed increased growth compared to wild-type, as well as bcl-2-transfected, WEHI7.2 cells. The trx- and bcl-2-transfected cell tumors both showed less spontaneous apoptosis than tumors formed by the wild-type cells. Unlike tumors formed by the wild-type and bcl-2-transfected WEHI7.2 cells, trx-transfected cell tumors did not show growth inhibition upon treatment with dexamethasone. This study suggests that increased thioredoxin expression in human cancers may result in an increased tumor growth through inhibition of spontaneous apoptosis and a decrease in the sensitivity of the tumor to drug-induced apoptosis.