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Angiotensin-(1-7) Reduces Prostate Cancer Growth and Metastasis by Altering the Tumor Microenvironment

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abstract
Ang-(1-7) is an endogenous peptide hormone that is produced in the circulation and in tissues by proteolytic cleavage of angiotensin I or II. The heptapeptide mediates biological responses by activating a unique G-protein-coupled angiotensin-(1-7) [AT(1-7)] receptor mas, thereby providing specific targeted actions when used as a therapeutic agent. In this study, athymic mice with human LNCaP xenografts were infused with saline or Ang-(1-7) (24 g/kg/h) for 54 days. The heptapeptide markedly reduced tumor volume and wet weight as compared to saline administration. Tumors from mice treated with Ang-(1-7) had a 78% reduction in Ki67 and a 55% decrease in the phosphorylation of the MAP kinases ERK1 and ERK2, compared to tumor tissue from Ang-(1-7)-medicated animals, suggesting that the heptapeptide reduces cell proliferation. A significant reduction in both LNCaP and PC3 cell growth was observed following incubation with 100 nM Ang-(1-7) in vitro, supporting the anti-proliferative properties of the heptapeptide. Mas was detected by Western blot hybridization in both cell types.
subject
Angiogenesis
Angiotensin-(1-7)
Metastasis
Prostate Cancer
sFlt-1
Vascular Endothelial Growth factor
contributor
Krishnan, Bhavani (author)
Tallant, Elisabeth. Ann (committee chair)
Dubey, Purnima (committee member)
Gallagher, Patricia E (committee member)
Lively, Mark O (committee member)
Daniel, Larry W (committee member)
date
2011-07-14T20:36:20Z (accessioned)
2011 (issued)
degree
Molecular Genetics & Genomics (discipline)
identifier
http://hdl.handle.net/10339/33490 (uri)
language
en (iso)
publisher
Wake Forest University
title
Angiotensin-(1-7) Reduces Prostate Cancer Growth and Metastasis by Altering the Tumor Microenvironment
type
Dissertation

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