KEAP1 and familial pancreatic carcinoma: Other possible mechanisms include: Keap1 down-regulation via promoter methylation, which has been described in lung cancer [36], transcriptional up-regulation of the NRF2 gene (which although not identified here in the pancreatic cancer cell lines, may nevertheless play a role in the tumors), dysregulation of Nrf2 ubiquitylation and proteasomal degradation, and stabilization of Nrf2 as a result of chronic oxidative stress.