Reactive oxygen species (ROS), by-products of aerobic respiration, promote 
genetic instability and contribute to the malignant transformation of cells. 
Among the genes related to ROS metabolism, Bach1 is a repressor of the oxidative 
stress response, and a negative regulator of ROS-induced cellular senescence 
directed by p53 in higher eukaryotes. While ROS are intimately involved in 
carcinogenesis, it is not clear whether Bach1 is involved in this process. We 
found that senescent Bach1-deficient mouse embryonic fibroblasts (MEFs) 
underwent spontaneous immortalization the same as did the wild-type cells. When 
transduced with constitutively active Ras (H-Ras(V12)), the proliferation and 
colony formation of these cells in vitro were markedly reduced. When 
transplanted into athymic nude mice, the growth and vascularization of tumors 
derived from Bach1-deficient cells were also decreased. Gene expression 
profiling of the MEFs revealed a new H-Ras(V12) signature, which was distinct 
from the previously reported signatures in epithelial tumors, and was partly 
dependent on Bach1. The Bach1-deficient cells showed diminished phosphorylation 
of MEK and ERK1/2 in response to H-Ras(V12), which was consistent with the 
alterations in the gene expression profile, including phosphatase genes. 
Finally, Bach1-deficient mice were less susceptible to 
4-nitroquinoline-1-oxidide (4-NQO)-induced tongue carcinoma than wild-type mice. 
Our data provide evidence for a critical role of Bach1 in cell transformation 
and tumor growth induced by activated H-Ras(V12).