Glucocorticoid eceptor dimerization in tumorigenesis

Glucocorticoids exert prominent effects in the colon, yet the role of glucocorticoid receptor (GR) dimerization remains unclear. AOM/DSS-induced tumorigenesis in GRdim mice harboring a predominantly monomeric GR was investigated. Monomeric GR activities in tumorigenesis followed a biphasic pattern. GRdim mice exhibited a delayed tumor onset and prolonged survival, yet tumors that did develop progressed more rapidly and grew larger. The distinct inflammatory gene signature in GRdim tumors resulted in impaired recruitment and activation of neutrophils and inflammatory macrophages, with Il1b as the central hub gene. GRdim tumor signature overlapped with genes dysregulated in human colorectal cancer and correlated with poor patient survival, thus mimicking the murine tumor model. Overall design: Colonic tumors were induced via AOM/DSS in wildtype (GRWT) and Glucocorticoid receptor (GR) dimerization deficient (GRDIM) mice. RNA from tumor tissue of both mouse strains was prepared and subsequently analysed by RNAseq profiling.