Decrypting the PAK4 transcriptome profile in mammary tumor forming cells using Next Generation Sequencing

Abstract

The p-21 Activated Kinase 4 (PAK4) protein kinase is implicated in many cancers, including breast cancer. Overexpression of PAK4 is sufficient to cause mouse mammary epithelial cells (iMMECs) to become tumorigenic. To gain insight into the long-term gene expression changes that occur downstream to PAK4, we performed Next Generation Sequencing of RNA collected from PAK4 overexpressing iMMECs and wild-type iMMECs. We identified a list of genes whose expression levels were altered in response to PAK4 overexpression in iMMECs. Some of these genes, including FoxC2 and ParvB, are consistent with a role for PAK4 in cancer. In addition, PAK4 regulates many genes that are frequently associated with the inflammatory response, raising the possibility that there is a connection between PAK4, inflammation, and the tumor microenvironment. This study delineates the PAK4 transcriptome profile in transformed mammary cells and can provide translational utility in other types of cancers as well.