arsenic-induced细胞转化和细胞凋亡的分子机制。
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arsenic-induced细胞转化和细胞凋亡的分子机制。
环境卫生教谕。2002年10月,110增刊5:757-9。
- PubMed ID
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12426127 (在PubMed]
- 文摘
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砷是证据确凿的人类致癌物与癌症相关的皮肤、肺、肝、膀胱。有趣的是,砷也被用作一种有效的化学治疗剂治疗人类癌症。然而,砷诱发癌细胞扩散的机制或癌症细胞死亡是不清楚。我们发现JB6 P +细胞的接触低浓度的砷诱导细胞转化,而更高浓度的砷诱导细胞凋亡。亚砷酸诱发的磷酸化细胞外signal-regulated蛋白激酶(erk)和c-Jun NH(2)终端激酶(物)。Arsenite-induced Erk激活被引入显性负显著抑制Erk2进入细胞,而表达的显性负Erk2没有抑制物或增殖蛋白激酶Erk激酶1/2。此外,arsenite-induced细胞转换被细胞中表达显性负Erk2。相反,过度的显性负JNK1增加细胞转换尽管它抑制arsenite-induced物激活。砷诱导AP-1和核转录因子k B (NF-kappaB)激活。阻塞NF-kappaB由显性负激活抑制性kappa Balpha抑制arsenic-induced细胞凋亡和增强arsenic-induced细胞转变。 Arsenic induced activation of JNKs at a similar dose range that was effective for induction of apoptosis in JB6 cells. In addition, we found that arsenic did not induce p53-dependent transactivation. Similarly, apoptosis induction was not different between p53 wild-type (p53(+/+)) or p53-deficient (p53(-/-)) cells. In contrast, arsenic-induced apoptosis was almost totally blocked by expression of a dominant-negative mutant of JNK. Taken together with previous findings that p53 mutations are involved in approximately 50% of all human cancers and nearly all chemotherapeutic agents kill cancer cells mainly by apoptotic induction, we suggest that arsenic may be a useful agent for the treatment of cancers with p53 mutations. These results suggest that the activation of Erks is required for arsenic-induced cell transformation, whereas the activation of JNKs and NF-kappaB is involved in arsenic-induced apoptosis of JB6 cells.