@misc{10481/77920,
year = {2021},
month = {10},
url = {https://hdl.handle.net/10481/77920},
abstract = {The glucocorticoid receptor NR3C1 is expressed in multiple cell types in the gut and
elsewhere. Intestinal epithelial cells both produce and respond to glucocorticoids in
different physiological and pathological contexts. In experimental colitis
glucocorticoids have been shown to exert a dual role, dampening inflammation while
producing a deterioration in animal status, including death. Mice with tamoxifen
inducible, intestinal epithelial specific deletion of NR3C1 (NR3C1IEC mice) are
protected against experimental colitis, suggesting glucocorticoid epithelial actions are
deleterious. Since glucocorticoids modulate epithelial proliferation it follows that they
may affect the development of colon cancer. In this study we set out to test this
hypothesis using the dextran sulfate sodium - azoxymethane model of colitis-associated
cancer. KO mice were found to exhibit a 2-fold higher tumor load but similar incidence
and tumor size. Tumors had a higher trend to extend to the submucosal layer (36% vs.
0%) in NR3C1IEC mice, and overexpressed Lgr5, Egfr and Myc, consistent with
increased proliferation and neoplastic transformation. Snai1 and Snai2 were upregulated
specifically in tumors of NR3C1ΔIEC mice, suggesting enhanced epithelial to
mesenchymal transition in the absence of the intestinal epithelial GC receptor. We
conclude that endogenous GC epithelial signaling is involved in colitis associated
cancer.},
organization = {This work was supported by funds from the Ministry of Economy and Competitivity,
partly with Fondo Europeo de Desarrollo Regional (FEDER) funds [SAF2017-88457-R,
AGL2017-85270-R, BFU2014-57736-P, AGL2014-58883-R] and by Junta de
Andalucía [CTS235, CTS164]. MA and CJA were supported by the University of
Granada (Contrato Puente Program - Plan Propio) and the Ministry of Education
[Spain], respectively. CIBERehd is funded by Instituto de Salud Carlos III.},
keywords = {glucocorticoid},
keywords = {azoxymethane},
keywords = {dextran sulfate sodium},
keywords = {intestinal steroidogenesis},
title = {Mice carrying an epithelial deletion of the glucocorticoid receptor NR3C1 develop a higher tumor load in experimental colitis associated cancer},
doi = {https://doi.org/10.1152/ajpgi.00384.2020},
author = {Arredondo Amador, María and González Pérez, Raquel and Aranda, Carlos J. and Martínez Augustín, María Olga and Sánchez De Medina López-Huertas, Fermín},
}