ERBB2 Regulates MED24 during Cancer Progression in Mice with Pten and Smad4 Deletion in the Pulmonary Epithelium
Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park (RTP), NC 27709, USA
Integrative Bioinformatics Support Group, NIEHS, RTP, NC 27709, USA
Integrated Laboratory Systems, Morrisville, NC 27560, USA
Authors to whom correspondence should be addressed.
Cells 2019, 8(6), 615; https://doi.org/10.3390/cells8060615
Received: 13 May 2019 / Revised: 11 June 2019 / Accepted: 18 June 2019 / Published: 19 June 2019
(This article belongs to the Special Issue Epidermal Growth Factor Receptor Signaling)
ERBB2 is an oncogenic driver with frequent gene mutations and amplification in human lung tumors and is an attractive target for lung cancer therapy. However, target therapies can be improved by understanding the in vivo mechanisms regulated by ERBB2 during lung tumor development. Here, we generated genetic mouse models to show that Erbb2 loss inhibited lung tumor development induced by deletion of Pten and Smad4. Transcriptome analysis showed that Erbb2 loss suppressed the significant changes of most of the induced genes by ablation of Pten and Smad4. Overlapping with ERBB2-associated human lung cancer genes further identified those ERBB2 downstream players potentially conserved in human and mouse lung tumors. Furthermore, MED24 was identified as a crucial oncogenic target of ERBB2 in lung tumor development. Taken together, ERBB2 is required for the dysregulation of cancer-related genes, such as MED24, during lung tumor development.