Item Details

title

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

author

Krishnan, Bhavani

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

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

type

Dissertation