Altered histone acetylation patterns in pancreatic cancer cell lines induce subtype-specific transcriptomic and phenotypic changes.
Background: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at advanced tumor stages with chemotherapy as the only treatment option. Large-scale gene expression studies have defined two major PDAC subtypes, a classical and basal-like, which differ in their response to chemotherapy. The transcriptional networks, which define the molecular PDAC subtypes, are regulated by epigenetic modifications. Given the reversible nature of the epigenome, we aim to determine if drug-induced epigenetic reprogramming of pancreatic cancer cells affects PDAC subtype identity and chemosensitivity. Overall design: Steady-state RNA measurement in varous PDAC cell lines with and without treatment