Innate immunity gene Nod2 protects mice from orthotopic breast cancer [post]

Serdar Gurses, Alisha Dziarski, Dipika Gupta
2022 unpublished
Nod2 is involved in innate immunity to bacteria, regulation of metabolism, and sensitivity to cancer. Nod2 polymorphism is associated with breast cancer, but the role of Nod2 in the development and progression of breast cancer is unknown. Here, we tested the hypothesis that Nod2 protects mice from breast cancer using the 4T1 orthotopic model of mammary tumorigenesis. We demonstrate that Nod2−/− mice have higher incidence and larger tumors than WT mice. Detailed analysis of the tumor
more » ... e showed that Nod2−/− mice had increased expression of genes that promote DNA replication and cell division and decreased expression of genes required for lipolysis, lipogenesis, and steroid biosynthesis compared with WT mice. Nod2−/− mice also had lower expression of genes required for adipogenesis and higher delipidation than WT mice. The tumors in Nod2−/− mice had decreased expression of genes associated with PPARα/γ signaling, increased activation of STAT3, decreased activation of STAT5, and no change in the activation of ERK compared with WT mice. Thus, we demonstrate that Nod2 protects mice from the 4T1 orthotopic breast tumor, and that tumors in Nod2−/− mice have higher DNA replication, cell cycling and delipidation than WT mice.
doi:10.21203/ fatcat:6zdj22a6r5ezfhe2ktu4oqn3am