Memminger, Martin and Keller, Max and Lopuch, Miroslaw and Pop, Nathalie and Bernhardt, Guenther and von Angerer, Erwin and Buschauer, Armin (2012) The Neuropeptide Y Y-1 Receptor: A Diagnostic Marker? Expression in MCF-7 Breast Cancer Cells Is Down-Regulated by Antiestrogens In Vitro and in Xenografts. PLOS ONE, 7 (12): e51032. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
The neuropeptide Y (NPY) Y-1 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 [H-3]-17 beta-estradiol and the Y1R selective antagonist [H-3]-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 Y(1)Rs was confirmed by confocal microscopy. The Y1R protein was up-regulated (100%) by 17 beta-estradiol (EC50 20 pM) and the predominant role of ER alpha was demonstrated by using the ER alpha-selective agonist "propylpyrazole triol". 17 beta-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 Y(1)Rs 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ESTROGEN-RECEPTOR; FUNCTIONAL EXPRESSION; PROGESTERONE-RECEPTOR; ADENYLATE-CYCLASE; ENDOCRINE THERAPY; HIGHLY POTENT; PEPTIDE-YY; ANTAGONIST; ALPHA; TARGETS; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Apr 2020 12:07 |
| Last Modified: | 30 Apr 2020 12:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17605 |
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