Reactive oxygen species and lung tumorigenesis by mutant K-ras:: A working hypothesis
Reactive oxygen species and lung tumorigenesis by mutant K-ras:: A working hypothesis
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DOI：
10.1080/01902140490495048
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发表时间：
2005-01-01
影响因子：
1.7
通讯作者：
Anderson, LM
中科院分区：
文献类型：
--
作者：
Maciag, A;Anderson, LM
野生型K-ras对小鼠肺内肿瘤有抑制作用，而突变型K-ras具有较强的致癌活性。因此，突变蛋白必须获得新的、显性的促肿瘤特性。活性氧物种的产生可能就是这样的特性之一。作者证明，在肺上皮细胞(E10)中，转导突变HK-ras(Va112)的细胞中的过氧化产物增加。DNA损伤的相关增加(彗星试验)与环氧合酶-2蛋白的增加相关。这种DNA损伤可被特定的环氧合酶-2抑制剂(SC58125)或细胞通透性修饰的过氧化氢酶完全消除。本文综述了ras诱导的活性氧和环氧合酶-2的产生，环氧合酶-2释放DNA损伤的活性氧，以及环氧合酶-2和活性氧在肺癌中的作用。
Wild-type K-ras is tumor suppressive in mouse lung, but mutant K-ras is actively oncogenic. Thus, the mutant protein must acquire new, dominant protumorigenic properties. Generation of reactive oxygen species could be one such property. The authors demonstrate increased peroxides in lung epithelial cells (E10)-transfected with mutant hK-ras(va112). An associated increase in DNA damage (comet assay) correlates with increased cyclooxygenase-2 protein. This DNA damage is completely abrogated by a specific cyclooxygenase-2 inhibitor (SC58125) or by a cell-permeable modified catalase. Literature is reviewed regarding generation of reactive oxygen and cyclooxygenase-2 induction by ras, cyclooxygenase-2 release of DNA-damaging reactive oxygen, and involvement Of cyclooxygenase-2 and reactive oxygen in lung cancer.