scholarly journals Orphan nuclear receptors in breast cancer pathogenesis and therapeutic response

2010 ◽  
Vol 17 (3) ◽  
pp. R213-R231 ◽  
Author(s):  
Rebecca B Riggins ◽  
Mary M Mazzotta ◽  
Omar Z Maniya ◽  
Robert Clarke
Keyword(s):  
Breast Cancer ◽  
Transcription Factors ◽  
Nuclear Receptors ◽  
Large Family ◽  
Orphan Receptor ◽  
Orphan Nuclear Receptors ◽  
Cancer Pathogenesis ◽  
Upstream Promoter ◽  
Carboxy Terminal ◽  
Gland Development

Nuclear receptors comprise a large family of highly conserved transcription factors that regulate many key processes in normal and neoplastic tissues. Most nuclear receptors share a common, highly conserved domain structure that includes a carboxy-terminal ligand-binding domain. However, a subgroup of this gene family is known as the orphan nuclear receptors because to date there are no known natural ligands that regulate their activity. Many of the 25 nuclear receptors classified as orphan play critical roles in embryonic development, metabolism, and the regulation of circadian rhythm. Here, we review the emerging role(s) of orphan nuclear receptors in breast cancer, with a particular focus on two of the estrogen-related receptors (ERRα and ERRγ) and several others implicated in clinical outcome and response or resistance to cytotoxic or endocrine therapies, including the chicken ovalbumin upstream promoter transcription factors, nerve growth factor-induced B, DAX-1, liver receptor homolog-1, and retinoic acid-related orphan receptor α. We also propose that a clearer understanding of the function of orphan nuclear receptors in mammary gland development and normal mammary tissues could significantly improve our ability to diagnose, treat, and prevent breast cancer.

scholarly journals Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1373 ◽  
Author(s):  
Herring ◽  
Elison ◽  
Tessem
Keyword(s):  
Transcription Factors ◽  
Family Member ◽  
Nuclear Receptors ◽  
Hormone Receptors ◽  
Cellular Proliferation ◽  
Nuclear Hormone Receptors ◽  
Fuel Utilization ◽  
Orphan Nuclear Receptors ◽  
Tissue Specific ◽  
Specific Effects

The Nr4a family of nuclear hormone receptors is composed of three members—Nr4a1/Nur77, Nr4a2/Nurr1 and Nr4a3/Nor1. While currently defined as ligandless, these transcription factors have been shown to regulate varied processes across a host of tissues. Of particular interest, the Nr4a family impinge, in a tissue dependent fashion, on cellular proliferation, apoptosis and fuel utilization. The regulation of these processes occurs through both nuclear and non-genomic pathways. The purpose of this review is to provide a balanced perspective of the tissue specific and Nr4a family member specific, effects on cellular proliferation, apoptosis and fuel utilization.

scholarly journals Nonhuman primate model in mammary gland biology and neoplasia research

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Fitriya N. Dewi ◽  
J. Mark Cline
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Nonhuman Primate ◽  
Nonhuman Primates ◽  
Breast Development ◽  
Primate Model ◽  
Cancer Pathogenesis ◽  
Important Field ◽  
Mammary Gland Biology ◽  
Gland Development

AbstractResearch on breast cancer pathogenesis, prevention and drug development remains an important field as this disease is still one of the leading causes of cancer death worldwide. Nonhuman primates, particularly macaque species, may serve as a highly translational animal model in breast cancer studies due to their similarity with humans in genetics, anatomy, reproductive and endocrine physiology including mammary gland development profile. The use of nonhuman primates in biomedical research, however, requires high ethical standards and an increasing expectation to improve strategies to replace, reduce and refine their use. Here, we discuss some key features of nonhuman primate mammary gland biology relevant to their strengths and limitations as models in studies of breast development and cancer risk.

scholarly journals SRC-3, a Steroid Receptor Coactivator: Implication in Cancer

2021 ◽  
Vol 22 (9) ◽  
pp. 4760
Author(s):  
Licen Li ◽  
Chu-Xia Deng ◽  
Qiang Chen
Keyword(s):  
Breast Cancer ◽  
Transcription Factors ◽  
Cancer Therapy ◽  
Nuclear Receptors ◽  
Essential Role ◽  
Transcriptional Activity ◽  
Steroid Receptor ◽  
Steroid Receptor Coactivator ◽  
Important Progress

Steroid receptor coactivator-3 (SRC-3), also known as amplified in breast cancer 1 (AIB1), is a member of the SRC family. SRC-3 regulates not only the transcriptional activity of nuclear receptors but also many other transcription factors. Besides the essential role of SRC-3 in physiological functions, it also acts as an oncogene to promote multiple aspects of cancer. This review updates the important progress of SRC-3 in carcinogenesis and summarizes its mode of action, which provides clues for cancer therapy.

Nuclear receptor atlas of female mouse liver parenchymal, endothelial, and Kupffer cells

2013 ◽  
Vol 45 (7) ◽  
pp. 268-275 ◽  
Author(s):  
Zhaosha Li ◽  
J. Kar Kruijt ◽  
Ronald J. van der Sluis ◽  
Theo J. C. Van Berkel ◽  
Menno Hoekstra
Keyword(s):  
Expression Pattern ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Kupffer Cells ◽  
Virgin Female ◽  
Orphan Receptor ◽  
Orphan Nuclear Receptors ◽  
Liver Parenchymal ◽  
Hepatic Expression ◽  
Parenchymal Cells

The liver consists of different cell types that together synchronize crucial roles in liver homeostasis. Since nuclear receptors constitute an important class of drug targets that are involved in a wide variety of physiological processes, we have composed the hepatic cell type-specific expression profile of nuclear receptors to uncover the pharmacological potential of liver-enriched nuclear receptors. Parenchymal liver cells (hepatocytes) and liver endothelial and Kupffer cells were isolated from virgin female C57BL/6 wild-type mice using collagenase perfusion and counterflow centrifugal elutriation. The hepatic expression pattern of 49 nuclear receptors was generated by real-time quantitative PCR using the NUclear Receptor Signaling Atlas (NURSA) program resources. Thirty-six nuclear receptors were expressed in total liver. FXR-α, EAR2, LXR-α, HNF4-α, and CAR were the most abundantly expressed nuclear receptors in liver parenchymal cells. In contrast, NUR77, COUP-TFII, LXR-α/β, FXR-α, and EAR2 were the most highly expressed nuclear receptors in endothelial and Kupffer cells. Interestingly, members of orphan receptor COUP-TF family showed a distinct expression pattern. EAR2 was highly and exclusively expressed in parenchymal cells, while COUP-TFII was moderately and exclusively expressed in endothelial and Kupffer cells. Of interest, the orphan receptor TR4 showed a similar expression pattern as the established lipid sensor PPAR-γ. In conclusion, our study provides the most complete quantitative assessment of the nuclear receptor distribution in liver reported to date. Our gene expression catalog suggests that orphan nuclear receptors such as COUP-TFII, EAR2, and TR4 may be of significant importance as novel targets for pharmaceutical interventions in liver.

Interplay between liganded and orphan nuclear receptors controls reproductive pathways

2000 ◽  
Vol 78 (3) ◽  
pp. 345-358 ◽  
Author(s):  
Raphaël Métivier ◽  
Yves Le Dréan ◽  
Gilles Salbert ◽  
Farzad Pakdel
Keyword(s):  
Estrogen Receptor ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Cell Fate ◽  
Nuclear Receptors ◽  
Gene Transcription ◽  
Transcription Rate ◽  
Orphan Nuclear Receptors ◽  
Estrogen Binding ◽  
Small Hydrophobic

Nuclear receptors are transcription factors that belong to an evolutionary ancient superfamily. These proteins, which are even present in primitive metazoans, are implicated in all levels of cell fate: proliferation, differentiation, and apoptosis. Some of these nuclear receptors behave as ligand-inducible transcription factors, as they have acquired during evolution the ability to bind ligands. This is the case for some proteins that recognize small hydrophobic signaling molecules, and particularly the estrogen receptor (ER or NR3A1), which regulates the target gene's transcription rate under estrogen binding. It is now known that the ER alone regulates the transcription of many genes, such as those implicated in reproductive functions. However, this ER-mediated signaling pathway could be modulated by other transcription factors. Our work has established that two other orphan nuclear receptors (SF-1 or NR5A1 and the COUP-TFs, NR2F1 and NR2F2) can enhance two ER-regulated genes implicated in salmonid reproductive functions: the ER gene itself, and the sGTHIIβ gene. Moreover, some xenoestrogens could disturb these regulations. Therefore, our data contribute to the concept that interplay between nuclear receptors is an important event for the transcriptional regulation of genes controlling cellular functions.Key words: reproduction, estrogen receptor, SF-1, COUP-TFI, gene transcription, xenobiotics.

scholarly journals Angiotensin-(1 - 7) and Human Chorionic Gonadotropin (hCG) Modulate the Nuclear Transcription Factors or Nuclear Receptors Genes in the Tumorigenic Undifferentiated Breast Cancer Cell Line SKBR3

2013 ◽  
Vol 04 (07) ◽  
pp. 70-74 ◽  
Author(s):  
Isidoro Binda Neto ◽  
Samuel Marcos Ribeiro de Noronha ◽  
Silvana Aparecida Alves Correa de Noronha ◽  
Maria Del Carmen Garcia Molina Wolgien ◽  
Alexandre Jesus Barros ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factors ◽  
Cell Line ◽  
Nuclear Receptors ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Chorionic Gonadotropin ◽  
Breast Cancer Cell Line ◽  
Human Chorionic Gonadotropin ◽  
Cancer Cell Line

scholarly journals Determinants of target gene specificity for ROR alpha 1: monomeric DNA binding by an orphan nuclear receptor.

1995 ◽  
Vol 15 (5) ◽  
pp. 2517-2526 ◽  
Author(s):  
V Giguère ◽  
L D McBroom ◽  
G Flock
Keyword(s):  
Dna Binding ◽  
Nuclear Receptors ◽  
Target Gene ◽  
Binding Studies ◽  
Orphan Nuclear Receptors ◽  
Retinoid Receptor ◽  
Amino Terminal ◽  
High Affinity ◽  
Carboxy Terminal ◽  
Terminal Domains

The ROR alpha isoforms are orphan members of the steroid/thyroid/retinoid receptor superfamily. Previous DNA-binding studies indicated that ROR alpha isoforms bind to response elements consisting of a single copy of the core recognition sequence AGGTCA preceded by a 6-bp A/T-rich sequence and that the distinct amino-terminal domains of each isoform influence DNA-binding specificity. In this report, we have investigated in detail the protein determinants of target gene specificity for the ROR alpha 1 isoform and have now identified the minimal sequence both in its amino- and carboxy-terminal domains required for high-affinity DNA binding. High-resolution methylation and ethylation interference analyses and mixing of truncated proteins in a DNA-binding assay show that ROR alpha 1 presumably binds along one face of the DNA helix as a monomer. By analogy to previous studies of the orphan receptors NGFI-B and FTZ-F1, extensive mutational analysis of the ROR alpha 1 protein shows that a domain extending from the carboxy-terminal end of the second conserved zinc-binding motif is required for specific DNA recognition. However, point mutations and domain swap experiments between ROR alpha 1 and NGFI-B demonstrated that sequence-specific recognition dictated by the carboxy-terminal extension is determined by distinct subdomains in the two receptors. These results demonstrate that monomeric nuclear receptors utilize diverse mechanisms to achieve high-affinity and specific DNA binding and that ROR alpha 1 represents the prototype for a distinct subfamily of monomeric orphan nuclear receptors.

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