RESUMO
Glucocorticoids (GCs) are anti-inflammatory and immunosuppressive steroid molecules secreted by the adrenal gland and regulated by the hypothalamic-pituitary-adrenal (HPA) axis. GCs present a circadian release pattern under normal conditions; they increase their release under stress conditions. Their mechanism of action can be via the receptor-independent or receptor-dependent pathway. The receptor-dependent pathway translocates to the nucleus, where the ligand-receptor complex binds to specific sequences in the DNA to modulate the transcription of specific genes. The glucocorticoid receptor (GR) and its endogenous ligand cortisol (CORT) in humans, and corticosterone in rodents or its exogenous ligand, dexamethasone (DEX), have been extensively studied in breast cancer. Its clinical utility in oncology has mainly focused on using DEX as an antiemetic to prevent chemotherapy-induced nausea and vomiting. In this review, we compile the results reported in the literature in recent years, highlighting current trends and unresolved controversies in this field. Specifically, in breast cancer, GR is considered a marker of poor prognosis, and a therapeutic target for the triple-negative breast cancer (TNBC) subtype, and efforts are being made to develop better GR antagonists with fewer side effects. It is necessary to know the type of breast cancer to differentiate the treatment for estrogen receptor (ER)-positive, ER-negative, and TNBC, to implement therapies that include the use of GCs.
Assuntos
Glucocorticoides , Neoplasias de Mama Triplo Negativas , Humanos , Glucocorticoides/uso terapêutico , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Dexametasona/farmacologia , Ligantes , Hidrocortisona/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismoRESUMO
The heat shock protein 90 kDalpha (Hsp90) subfamily is constituted by five isoforms, among them Hsp90alpha and Hsp90beta are the more abundant cytosolic proteins. These two proteins are molecular chaperons that participate in numerous cellular processes, through interacting with more than 100 proteins known as client proteins of Hsp90. These client proteins include: transcriptional factors, kinase proteins and other proteins that participate in transcriptional and transductional regulation such as steroid hormone receptors and nitric oxide synthases. This review offers a retrospective in the recent information about molecular and cellular functions of Hsp90 in the vascular physiology. In addition, the studies that evaluate Hsp90 role in the renal physiology and pathophysiology are discussed. Finally, the molecular tools developed to manipulate the Hsp90 expression in vitro and in vivo, through its inhibition or over-expression are reviewed. All these studies together have allowed increasing our knowledge regarding the role of Hsp90 during normal and pathophysiological conditions.