Cancers and is often associated with poor prognosis MIG-6 down-regulation in Th-1165a non-small cell lung cancer is associated with increased EGFR signaling and order 517-28-2 poorly differentiated cancer, while loss of its expression in ErbB2-amplified breast carcinoma renders the cancer cells more resistant to Herceptin, the neutralizing antibody against ErbB2. In glioblastoma, MIG-6 is identified as a single gene within the most commonly deleted region at the 1p36.23 locus, and its expression is down-regulated in 34 of glioblastoma samples. While MIG-6 down-regulation is reported in a high percentage of papillary thyroid cancers, high MIG-6 expression correlates with longer survival and is associated with favorable surgical outcomes for those patients. Decreased MIG-6 expression has also been reported in skin cancer, endometrial cancer, and hepatocellular carcinomas. Moreover, even though such events are rare, three mutations in the MIG-6 gene have been identified in human lung cancer and one in neuroblastoma. Further evidence supporting MIG-6 as a tumor suppressor gene arose from mouse studies; Mig-6- deficient mice are prone to develop epithelial hyperplasia or tumors in organs including the lung, skin, uterus, gallbladder, and bile duct. Epigenetic alteration, one of the most well-known mechanisms leading to inactivation of a tumor suppressor gene, can result from DNA methylation or histone deacetylation in the genes promoter. Given that down-regulation of MIG-6 is frequently observed in many human cancers, we asked whether MIG-6 expression was affected by DNA methylation and histone deacetylation. Here, we show that the MIG-6 promoter itself is neither hypermethylated nor affected by histone deacetylation. However, its expression is induced by the DNA methyltransferase inhibitor 5-aza-29-deoxycytidine in melanoma cell lines and by the histone deacetylase inhibitor trichostatin A in lung cancer lines. By dissecting its promoter regulatory region using a luciferase reporter assay, we identified a minimal TSA-response element in exon 1 of MIG-6 that is essential for its induction by TSA in lung cancer cells. To our surprise, we found that TSA treatment significantly increased the amount of MIG-6 protein in the lung cancer cell lines, but not in the melanoma lines. In contrast,