OVER-EXPRESSION OF HSP70 CONFERS TUMORIGENICITY TO MOUSE FIBROSARCOMA CELLS
OVER-EXPRESSION OF HSP70 CONFERS TUMORIGENICITY TO MOUSE FIBROSARCOMA CELLS
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DOI：
10.1002/ijc.2910600520
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发表时间：
1995-03-03
影响因子：
6.4
通讯作者：
JAATTELA, M
中科院分区：
文献类型：
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作者：
JAATTELA, M
主要的热休克蛋白HSP70在WEHI-S肿瘤细胞中过表达，使其对肿瘤坏死因子的细胞毒作用具有抵抗力。为了研究这种耐药性在体内的意义，研究了转染人HSP70的WEHI-S细胞在裸鼠和正常同系小鼠中的正、反义定向致瘤作用。在裸鼠体内，HSP70的表达水平与肿瘤的致瘤性显著相关。HSP70的表达使WEHI细胞在正常小鼠中也发生肿瘤，但与无瘤小鼠相比，形成肿瘤所需的细胞数量更多。热休克蛋白70在WEHI-S细胞中的过表达不能增强其体外贴壁依赖性生长或在软琼脂中形成集落的能力。HSP70转基因细胞在体外对小鼠天然细胞毒细胞和巨噬细胞的杀伤能力显著增强。用肿瘤坏死因子延长培养的WEHI-S细胞，也可以独立于热休克蛋白70诱导出类似的致瘤表型。这些结果表明，热休克蛋白70的过表达增加了WEHI-S细胞在小鼠体内的致瘤潜能，使这些细胞逃避了早期肿瘤坏死因子介导的抗肿瘤免疫监视。(C)1995年Wiley-Liss公司
Over-expression of the major heat-shock protein hsp70 in WEHI-S tumor cells renders them resistant to the cytotoxic effects of tumor necrosis factor (TNF). To study the significance of this resistance in vivo, the tumorigenic potential of WEHI-S cells transfected with human hsp70 in sense and anti-sense orientation was investigated in athymic and in normal syngenic mice. A striking correlation was observed between the level of hsp70 expression and tumorigenicity in athymic mice. Hsp70 expression rendered WEHI cells tumorigenic also in normal mice, but higher numbers of cells were required for tumor formation than in athymic mice. Over-expression of hsp70 in WEHI-S cells did not enhance their anchorage-dependent growth in vitro or their ability to form colonies in soft agar. The hsp70-transfected cells exhibited greatly increased resistance against killing by murine natural cytotoxic cells and macrophages in vitro. A similar tumorigenic phenotype could also be induced independently of hsp70 by prolonged culture of WEHI-S cells with TNF. These results suggest that over-expression of hsp70 increases the tumorigenic potential of WEHI-S cells in mice, by allowing these cells to escape from the early TNF-mediated anti-tumor immune surveillance. (C) 1995 Wiley-Liss, Inc.