The Aryl Hydrocarbon (Dioxin) Receptor/Transcription Factor and Cytochrome P450 1B1 as Targets for Breast Cancer Immunotherapy

2002 ◽  
Author(s):  
David H. Sherr
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cytochrome P450 ◽  
Cancer Immunotherapy ◽  
Cytochrome P450 1B1 ◽  
Aryl Hydrocarbon ◽  
Dioxin Receptor

Genistein Induces Cytochrome P450 1B1 Gene Expression and Cell Proliferation in Human Breast Cancer MCF-7 Cells

2015 ◽  
Vol 34 (2) ◽  
pp. 153-159 ◽  
Author(s):  
Yinan K. Wei ◽  
Irene Gamra ◽  
Andrew Davenport ◽  
Richard Lester ◽  
Lijun Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Proliferation ◽  
Cytochrome P450 ◽  
Human Breast Cancer ◽  
Human Breast ◽  
Cytochrome P450 1B1 ◽  
Mcf 7

scholarly journals Bioengineering of Genetically Encoded Gene Promoter Repressed by the Flavonoid Apigenin for Constructing Intracellular Sensor for Molecular Events

Biosensors ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 137
Author(s):  
Nicole M. Desmet ◽  
Kalyani Dhusia ◽  
Wenjie Qi ◽  
Andrea I. Doseff ◽  
Sudin Bhattacharya ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cytochrome P450 ◽  
Synthetic Biology ◽  
Electronic Devices ◽  
Gene Promoter ◽  
Transcription Level ◽  
Response Elements ◽  
Aryl Hydrocarbon ◽  
Molecular Events ◽  
Cytochrome P450 Family

In recent years, Synthetic Biology has emerged as a new discipline where functions that were traditionally performed by electronic devices are replaced by “cellular devices”; genetically encoded circuits constructed of DNA that are built from biological parts (aka bio-parts). The cellular devices can be used for sensing and responding to natural and artificial signals. However, a major challenge in the field is that the crosstalk between many cellular signaling pathways use the same signaling endogenous molecules that can result in undesired activation. To overcome this problem, we utilized a specific promoter that can activate genes with a natural, non-toxic ligand at a highly-induced transcription level with low background or undesirable off-target expression. Here we used the orphan aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that upon activation binds to specific AHR response elements (AHRE) of the Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) promoter. Flavonoids have been identified as AHR ligands. Data presented here show the successful creation of a synthetic gene “off” switch that can be monitored directly using an optical reporter gene. This is the first step towards bioengineering of a synthetic, nanoscale bio-part for constructing a sensor for molecular events.

scholarly journals Upregulation of Aryl Hydrocarbon Receptor in Granulosa Cells by Endoplasmic Reticulum Stress Contributes to the PCOS Pathophysiology

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A773-A773
Author(s):  
Chisato Kunitomi ◽  
Miyuki Harada ◽  
Jerilee M K Azhary ◽  
Akari Kusamoto
Keyword(s):  
Endoplasmic Reticulum ◽  
Cytochrome P450 ◽  
Er Stress ◽  
Aryl Hydrocarbon Receptor ◽  
Granulosa Cells ◽  
Target Gene ◽  
Downstream Signaling ◽  
Cytochrome P450 1B1 ◽  
Aryl Hydrocarbon

Abstract Studies have demonstrated that endocrine disrupting chemicals (EDC) are involved in the pathophysiology of PCOS, and aryl hydrocarbon receptor (AHR) mediates the cellular effect of EDC by inducing xenobiotic metabolizing enzymes including cytochrome P450 1B1 (CYP1B1). However, recent studies suggest the novel role of AHR in various diseases, including obesity and cancer progression, independent from the EDC metabolism. We previously demonstrated that endoplasmic reticulum (ER) stress, a newly recognized local factor, contributes to PCOS pathology by affecting diverse functions of granulosa cells. We hypothesized that ER stress induces the expression of AHR and activates its downstream signaling in granulosa cells, irrespective of the presence of EDCs, thereby promoting PCOS pathogenesis. At first, we determined the upregulation of AHR, AHR nuclear translocator (ARNT), and AHR target gene cytochrome P450 1B1 (CYP1B1) in the granulosa cells of PCOS patients and model mice by immunohistochemical staining and qPCR. We examined CYP1B1 as a representative AHR target gene. Treatment of cultured human granulosa-lutein cells (GLCs) with tunicamycin (ER stress inducer) upregulated the expression of AHR, ARNT and CYP1B1. Knockdown of AHR decreased the tunicamycin-induced expression and activity of CYP1B1, suggesting the intermediary role of AHR in upregulation of AHR activity by ER stress. To confirm the role of AHR in vivo, we administered the AHR antagonist CH223191 to PCOS model mice. The administration of the antagonist restored estrous cycling and decreased the number of atretic antral follicles, concomitant with downregulation of AHR and CYP1B1 in granulosa cells. Taken together, this study indicates that AHR and downstream signaling are activated by ER stress in GLCs of PCOS. Moreover, downregulation of local AHR expression and activation restores a normal reproductive phenotype in a PCOS mouse model. Our findings demonstrate that AHR activated by ER stress in the follicular microenvironment contributes to PCOS pathology, and that AHR represents a novel therapeutic target for PCOS.

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