E47 Governs the MYC-CDKN1B/p27^KIP1-RB Network to Growth Arrest PDA Cells Independent of CDKN2A/p16^INK4A and Wild-Type p53.

ABSTRACT:

Background & aims

Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16^INK4A, and SMAD4, drive progression of pancreatic ductal adenocarcinoma (PDA). Overexpression of MYC and deregulation of retinoblastoma (RB) further promote cell proliferation and make identifying a means to therapeutically alter cell-cycle control pathways in PDA a significant challenge. We previously showed that the basic helix-loop-helix transcription factor E47 induced stable growth arrest in PDA cells in vitro and in vivo. Here, we identified molecular mechanisms that underlie E47-induced growth arrest in low-passage, patient-derived primary and established PDA cell lines.

Methods

RNA sequencing was used to profile E47-dependent transcriptomes in 5 PDA cell lines. Gene

SUBMITTER: Scully KM 

PROVIDER: S-EPMC6039985 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature