Reactive oxygen species and lung tumorigenesis by mutant K-ras: a working hypothesis.
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
Maciag
Anna
A
Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
Anderson
Lucy M
LM
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D051546:Cyclooxygenase 2; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D009154:Mutation / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*
D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases