A truncated Ah receptor blocks the hypoxia and estrogen receptor signaling pathways: a viable approach for breast cancer treatment.

A truncated Ah receptor blocks the hypoxia and estrogen receptor signaling pathways: a viable approach for breast cancer treatment. Research Abstract Details 

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A truncated Ah receptor blocks the hypoxia and estrogen receptor signaling pathways: a viable approach for breast cancer treatment. Abstract Text:

Kyle A Jensen,Tony C Luu,William K Chan,

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which requires heterodimerization with the Ah receptor nuclear translocator (Arnt) for function. Arnt is also a dimerization partner of the hypoxia inducible factor 1alpha (HIF-1alpha) for the hypoxia signaling. Additionally, Arnt is found to be a potent coactivator of the estrogen receptor (ER) signaling. Thus we examined whether the presence of an increased amount of AhR may suppress both the HIF-1alpha and ER signaling pathways by sequestering Arnt. We tested our hypothesis using a human AhR construct C Delta553 which is capable of heterodimerizing with Arnt in the absence of a ligand. Transient transfection studies using a corresponding luciferase reporter plasmid in MCF-7 cells showed that C Delta553 effectively suppressed the AhR, HIF-1alpha, and ER signaling pathways. Reverse transcription/real-time QPCR data showed that C Delta553 blocked the up-regulation of the target genes controlled by AhR (CYP1A1), HIF-1alpha (VEGF, aldolase C, and LDH-A), and ER (GREB1, pS2, and c-myc) in MCF-7 cells. Since both HIF-1alpha and ER are highly active in the ER-positive breast cancer, C Delta553 has the potential to be developed as a protein drug to treat breast cancer by blocking these two signaling pathways.

A truncated Ah receptor blocks the hypoxia and estrogen receptor signaling pathways: a viable approach for breast cancer treatment. Publishing Authors By Initials

KA Jensen,TC Luu,WK Chan,

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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A truncated Ah receptor blocks the hypoxia and estrogen receptor signaling pathways: a viable approach for breast cancer treatment. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular pharmaceutics

VOLUME: 3

Page Numbers: 695-703

Journal Abbreviation: Mol. Pharm.

ISSN: 1543-8384

DAY: 3

MONTH: 12

YEAR: 2007

A truncated Ah receptor blocks the hypoxia and estrogen receptor signaling pathways: a viable approach for breast cancer treatment. Information

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LANGUAGE: eng

NlmUniqueID: 101197791

A truncated Ah receptor blocks the hypoxia and estrogen receptor signaling pathways: a viable approach for breast cancer treatment. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: genetics

Chemical & Substance for Abstract: A truncated Ah receptor blocks the hypoxia and estrogen receptor signaling pathways: a viable approach for breast cancer treatment. Information

Substance Name: Luciferases

Registry Number: EC 1.13.12.-

Grant and Affiliation Information for A truncated Ah receptor blocks the hypoxia and estrogen receptor signaling pathways: a viable approach for breast cancer treatment.

AFFILIATION: Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California 95211, USA.

Country: United States

AGENCY: United States NIEHS

GRANT: ES09794

ACRONYM: ES

MEDLINETA: Mol Pharm

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