Related Experiment Video
Updated: Apr 16, 2026
A Chemical Screening Procedure for Glucocorticoid Signaling with a Zebrafish Larva Luciferase Reporter System
Published on: September 10, 2013
Genomic and non-genomic effects of glucocorticoids: implications for breast cancer
Irma B Mitre-Aguilar1, Alberto J Cabrera-Quintero1, Alejandro Zentella-Dehesa2
1Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) México D. F., México ; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Auntónoma de México (UNAM) México D. F., México.
Abstract:
Glucocorticoids (GC) are essential steroid hormones for human life. They regulate a series of important processes by binding with three glucocorticoid receptors (GR) and activating genomic and non-genomic pathways. Activated cytoplasmic GR can directly bind DNA and transactivate or transrepress specific genes. Additionally, it can interact with other transcription factors to affect gene expression indirectly. The two membrane GR can interact with mitogen-activated protein (MAP) kinases or activate cAMP and Ca(2+)-dependent pathways, respectively. Glucocorticoids have been widely used as co-treatment of patients with breast cancer (BC) due to reduction of chemotherapy-induced side effects such as nausea, lack of appetite, and inflammation. However, GC may exert a direct effect on tumor response to chemotherapy. In vitro, GC inhibits chemotherapy, radiation and cytokine-induced apoptosis by upregulating antiapoptotic genes and detoxifying proteins. They also upregulate the proto-oncogene c-fms, tumor suppressor gene Nm23, several members of the epidermal growth factor (EGF) signaling pathway and the estrogen sulfotransferase signaling pathway, thus indirectly inhibiting estrogen receptor activation. They inhibit the proangiogenic gene (vascular endothelial growth factor (VEGF); Therefore, they could play a role in reducing angiogenesis. Interestingly, the phosphorylation status of ser-211 in the GR is dependent on the expression of the BRCA1 gene, a tumor suppressor gene that is mutated in the majority of patients with triple negative BC. Some clinical randomized trials have also attempted to address the effect of GC on patients with BC. Thus, in this review we summarize GC mechanisms of action and their participation in several facets of BC.
Insights
Glucocorticoids (GC) are vital hormones used in breast cancer (BC) treatment to manage side effects. However, they can also impact chemotherapy efficacy by influencing apoptosis and tumor growth pathways.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Glucocorticoids (GC) are essential steroid hormones regulating vital physiological processes via glucocorticoid receptors (GR).
- GC are co-administered in breast cancer (BC) therapy to mitigate chemotherapy side effects like nausea and inflammation.
- Emerging evidence suggests GC may directly influence BC treatment outcomes.
Purpose of the Study:
- To review the multifaceted mechanisms of glucocorticoid action.
- To elucidate the role of GC in various aspects of breast cancer progression and treatment response.
Main Methods:
- Review of existing literature on GC signaling pathways (genomic and non-genomic).
- Analysis of in vitro studies detailing GC effects on apoptosis, gene expression, and signaling pathways relevant to BC.
- Consideration of clinical trial data investigating GC use in BC patients.
Main Results:
- GC activate cytoplasmic and membrane GR, influencing gene transcription and signaling cascades.
- In vitro, GC can inhibit chemotherapy, radiation, and cytokine-induced apoptosis.
- GC modulate genes involved in growth factor signaling, estrogen pathways, and angiogenesis, potentially impacting BC.
- BRCA1 gene expression influences GR phosphorylation, relevant to triple-negative BC.
Conclusions:
- Glucocorticoids possess complex roles in breast cancer, affecting both treatment side effects and direct anti-tumorigenic or pro-tumorigenic activities.
- Understanding these dual actions is crucial for optimizing GC use in breast cancer management.
- Further clinical investigation is warranted to fully delineate the impact of GC on breast cancer prognosis.
Related Concept Videos
01:22Target Cell Response to Hormones
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
01:31Hormones of the Adrenal Glands
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...
01:29Pharmacogenetics and Pharmacogenomics: Overview
01:25Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...