The Neuropeptide Y Y1 receptor: a diagnostic marker? Expression in MCF-7 breast cancer cells is down-regulated by antiestrogens in vitro and in xenografts

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urn:nbn:de:bvb:355-epub-265783 Copy

Memminger, Martin ; Keller, Max ; Lopuch, Miroslaw ; Pop, Nathalie ; Bernhardt, Günther ; von Angerer, Erwin ; Buschauer, Armin

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Date of publication of this fulltext: 30 Oct 2012 15:02

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Details

Item type:	Article
Date:	7 December 2012
Institutions:	Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer)
Projects:	GRK 760, Graduiertenkolleg Medizinische Chemie, Open Access Publizieren (DFG)
Identification Number:	Value Type 10.1371/journal.pone.0051032 DOI 23236424 PubMed ID
Keywords:	neuropeptide Y; Y1 receptor; G-protein coupled receptor; estrogen receptor; imaging; MCF-7 breast cancer; xenograft; nude mice; autoradiography; radioligand; [3H]-UR-MK114; argininamides; antiestrogen; tamoxifen; diagnostic marker
Dewey Decimal Classification:	500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences 600 Technology > 615 Pharmacy
Status:	Published
Refereed:	Yes, this version has been refereed
Created at the University of Regensburg:	Yes
Item ID:	26578

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Abstract

The neuropeptide Y (NPY) Y1 receptor (Y1R) has been suggested as a tumor marker for in vivo imaging and as a therapeutic target. In view of the assumed link between estrogen receptor (ER) and Y1R in mammary carcinoma and with respect to the development of new diagnostic tools we investigated the Y1R protein expression in human MCF-7 cell variants differing in ER content and sensitivity against ...

Abstract

The neuropeptide Y (NPY) Y1 receptor (Y1R) has been suggested as a tumor marker for in vivo imaging and as a therapeutic target. In view of the assumed link between estrogen receptor (ER) and Y1R in mammary carcinoma and with respect to the development of new diagnostic tools we investigated the Y1R protein expression in human MCF-7 cell variants differing in ER content and sensitivity against antiestrogens. ER and Y1R expression were quantified by radioligand binding using [3H]-17beta-estradiol and the Y1R selective antagonist [3H]-UR-MK114, respectively. The latter was used for cellular binding studies and for autoradiography of MCF-7 xenografts. The fluorescent ligands Cy5-pNPY (universal Y1R, Y2R and Y5R agonist) and UR-MK22 (selective Y1R antagonist), as well as the selective antagonists BIBP3226 (Y1R), BIIE0246 (Y2R) and CGP71683 (Y5R) were used to identify the NPY receptor subtype(s) by confocal microscopy. Y1R functionality was determined by mobilization of intracellular Ca2+. Sensitivity of MCF-7 cells against antiestrogen 4-hydroxytamoxifen correlated directly with the ER content. The exclusive expression of Y1Rs was confirmed by confocal microscopy. The Y1R protein was up-regulated (100 %) by 17beta-estradiol (EC50 20 pM) and the predominant role of ERalpha was demonstrated by using the ERalpha-selective agonist “propylpyrazole triol”. 17beta-Estradiol-induced over-expression of functional Y1R protein was reverted by the antiestrogen fulvestrant (IC50 5 nM) in vitro. Furthermore, tamoxifen treatment of nude mice resulted in an almost total loss of Y1Rs in MCF-7 xenografts. In conclusion, the value of the Y1R as a target for therapy and imaging in breast cancer patients may be compromised due to Y1R down-regulation induced by hormonal (antiestrogen) treatment.

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Metadata last modified: 02 Jun 2018 20:12

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