Clinical and Genomic Crosstalk between Glucocorticoid Receptor and Estrogen Receptor α In Endometrial Cancer
Jeffery M. Vahrenkamp,
Chieh-Hsiang Yang,
Adriana C. Rodriguez,
Aliyah Almomen,
Kristofer C. Berrett,
Alexis N. Trujillo,
Katrin P. Guillen,
Bryan E. Welm,
Elke A. Jarboe,
Margit M. Janat-Amsbury,
Jason Gertz
Affiliations
Jeffery M. Vahrenkamp
Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
Chieh-Hsiang Yang
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT 84112, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA
Adriana C. Rodriguez
Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
Aliyah Almomen
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT 84112, USA; College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia
Kristofer C. Berrett
Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
Alexis N. Trujillo
University of New Mexico, Albuquerque, NM 87131, USA
Katrin P. Guillen
Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
Bryan E. Welm
Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Surgery, University of Utah, Salt Lake City, UT 84112, USA
Elke A. Jarboe
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
Margit M. Janat-Amsbury
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT 84112, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA; Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA
Jason Gertz
Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Corresponding author
Summary: Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each other’s function. Estrogen receptor α (ER) and glucocorticoid receptor (GR) are expressed in the uterus, and their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic-binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is altered significantly by estradiol with GR recruited to ER-bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol but with additional regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer. : Estrogen receptor α (ER) and glucocorticoid receptor (GR) are expressed in the uterus and have differential effects on growth. Vahrenkamp et al. find that expression of both receptors is associated with poor outcome in endometrial cancer and that simultaneous induction of ER and GR leads to molecular interplay between the receptors. Keywords: estrogen receptor, glucocorticoid receptor, endometrial cancer
