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Breast Cancer Research
Published in: Breast Cancer Research 3/2009

Open Access 01-06-2009 | Research article

Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer

Authors: Ruben Rene Gonzalez, Amber Watters, Yanbo Xu, Udai P Singh, David R Mann, Bo R Rueda, Manuel L Penichet

Published in: Breast Cancer Research | Issue 3/2009

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Abstract

Introduction

We have shown previously that treatment with pegylated leptin peptide receptor antagonist 2 (PEG-LPrA2) reduced the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor type 2 (VEGFR2) and growth of 4T1-breast cancer (BC) in syngeneic mice. In this investigation, PEG-LPrA2 was used to evaluate whether the inhibition of leptin signaling has differential impact on the expression of pro-angiogenic and pro-proliferative molecules and growth of human estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) BC xenografts hosted by immunodeficient mice.

Methods

To test the contribution of leptin signaling to BC growth and expression of leptin-targeted molecules, PEG-LPrA2 treatment was applied to severe immunodeficient mice hosting established ER+ (MCF-7 cells; ovariectomized/supplemented with estradiol) and ER- (MDA-MB231 cells) BC xenografts. To further assess leptin and PEG-LPrA2 effects on ER+ and ER- BC, the expression of VEGF and VEGFR2 (protein and mRNA) was investigated in cell cultures.

Results

PEG-LPrA2 more effectively reduced the growth of ER+ (>40-fold) than ER- BC (twofold) and expression of pro-angiogenic (VEGF/VEGFR2, leptin/leptin receptor OB-R, and IL-1 receptor type I) and pro-proliferative molecules (proliferating cell nuclear antigen and cyclin D1) in ER+ than in ER- BC. Mouse tumor stroma in ER+ BC expressed high levels of VEGF and leptin that was induced by leptin signaling. Leptin upregulated the transcriptional expression of VEGF/VEGFR2 in MCF-7 and MDA-MB231 cells.

Conclusions

These results suggest that leptin signaling plays an important role in the growth of both ER+ and ER- BC that is associated with the leptin regulation of pro-angiogenic and pro-proliferative molecules. These data provide support for the potential use of leptin-signaling inhibition as a novel treatment for ER+ and ER- BC.
Appendix
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Metadata
Title
Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer
Authors
Ruben Rene Gonzalez
Amber Watters
Yanbo Xu
Udai P Singh
David R Mann
Bo R Rueda
Manuel L Penichet
Publication date
01-06-2009
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2009
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2321

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