title: Glucocorticoid receptor signaling and prostate cancer.
abstract: Glucocorticoids (GCs) are provided to hormone-refractory prostate cancer (HRPC) patients partly due to the inhibitory effects on adrenal androgen production acting as a pituitary suppressant. Nowadays, the combination of chemotherapy and dexamethasone is a standard treatment for HRPC patients while increasing evidence suggests that a lot of local tissue factors like growth factors, angiogenic/lymphogenic factors, apoptosis-related factors, cytokines related to the transition of prostate cancer from androgen dependence to hormone-refractory status, are among the targets of GR signaling. However, although glucocorticoids have been recognized to be one of a limited number of treatment options for HRPC, the molecular basis of GC-induced effects in prostate cancer remains poorly defined. In this review, we focus on how GCs induce effects via the GR-mediated transcriptional regulation of specific genes known to play key roles in cellular/tissue functions, including growth, apoptosis, inflammation, metastasis, differentiation, cell survival and angiogenesis. In our effort to unravel the molecular interplay of GR signaling with other signaling cascades prevalent in prostate cancer, we also include a detailed description of GR gene and protein structure/function and provide the knowledge gained recently into the mechanism(s) of the cross talk between GR and other signaling cascades via which GCs exert their multiple effects.
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, 75 M. Asias, Goudi, 11527 Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Kassi
authors.forename: P
authors.initials: P
authors.lastname: Moutsatsou
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018931:Antineoplastic Agents, Hormonal; D005938:Glucocorticoids; D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone