ANGIOTENSIN-(1-7): A NOVEL SMALL MOLECULE FOR THE TARGETED TREATMENT OF TRIPLE NEGATIVE BREAST CANCER
type: CreativeWork
description: ABSTRACT Soto-Pantoja, David Ricardo ANGIOTENSIN-(1-7): A NOVEL SMALL MOLECULE FOR THE TARGETED TREATMENT OF TRIPLE NEGATIVE BREAST CANCER Dissertation under the direction of E. Ann Tallant, Ph.D., Professor and Patricia E. Gallagher Ph.D., Associate Professor Triple negative breast cancer (TNBC), an aggressive breast tumor that disproportionately affects young and minority women, is associated with a poor survival rate regardless of stage at diagnosis due to development of distant metastases. Tumors from women with TNBC lack estrogen receptors and progesterone receptors and have basal expression of the human epidermal growth factor receptor 2 (HER2), severely limiting therapeutic strategies. The purpose of this study was to determine whether angiotensin-(1-7) [Ang-(1-7)], an endogenous peptide hormone that activates the AT(1-7) receptor mas, inhibits the growth of triple negative breast cancer cells and tumors and identify the molecular mechanisms for the inhibition of cancer cell growth. Injection of MDA-MB-231 cells into the mammary fat pad of athymic mice resulted in triple negative breast tumors that were treated for 28 days with either saline or Ang-(1-7). The average tumor volume from mice treated with the heptapeptide was approximately 3-fold less than the size of tumors from control animals (170.8 ± 21.4 mm3 vs. 546.7 ± 87.9 mm3; n = 5, p < 0.05) and tumor weight was reduced from 1.0 ± 0.2 g in the saline-treated mice to 0.5 ± 0.1 g in Ang-(1-7)-treated mice (n = 5, p < 0.05). The reduced size of Ang-(1-7)-treated tumors was associated with low immunoreactivity to Ki67, a proliferation marker (84.2 ± 8.2 compared to 41 ± 7.6), suggesting that Ang-(1-7) attenuates cell growth. Activity of the MAP kinases ERK1 and ERK2 was reduced in tumors of Ang-(1-7)-treated mice which was associated with a receptor-mediated increase in the MAP kinase phosphatase DUSP1 (1.01 ± 0.1 relative gene expression in tumors from saline-treated mice compared to 1.78 ± 0.13 in tumors…
abstract: ABSTRACT Soto-Pantoja, David Ricardo ANGIOTENSIN-(1-7): A NOVEL SMALL MOLECULE FOR THE TARGETED TREATMENT OF TRIPLE NEGATIVE BREAST CANCER Dissertation under the direction of E. Ann Tallant, Ph.D., Professor and Patricia E. Gallagher Ph.D., Associate Professor Triple negative breast cancer (TNBC), an aggressive breast tumor that disproportionately affects young and minority women, is associated with a poor survival rate regardless of stage at diagnosis due to development of distant metastases. Tumors from women with TNBC lack estrogen receptors and progesterone receptors and have basal expression of the human epidermal growth factor receptor 2 (HER2), severely limiting therapeutic strategies. The purpose of this study was to determine whether angiotensin-(1-7) [Ang-(1-7)], an endogenous peptide hormone that activates the AT(1-7) receptor mas, inhibits the growth of triple negative breast cancer cells and tumors and identify the molecular mechanisms for the inhibition of cancer cell growth. Injection of MDA-MB-231 cells into the mammary fat pad of athymic mice resulted in triple negative breast tumors that were treated for 28 days with either saline or Ang-(1-7). The average tumor volume from mice treated with the heptapeptide was approximately 3-fold less than the size of tumors from control animals (170.8 ± 21.4 mm3 vs. 546.7 ± 87.9 mm3; n = 5, p < 0.05) and tumor weight was reduced from 1.0 ± 0.2 g in the saline-treated mice to 0.5 ± 0.1 g in Ang-(1-7)-treated mice (n = 5, p < 0.05). The reduced size of Ang-(1-7)-treated tumors was associated with low immunoreactivity to Ki67, a proliferation marker (84.2 ± 8.2 compared to 41 ± 7.6), suggesting that Ang-(1-7) attenuates cell growth. Activity of the MAP kinases ERK1 and ERK2 was reduced in tumors of Ang-(1-7)-treated mice which was associated with a receptor-mediated increase in the MAP kinase phosphatase DUSP1 (1.01 ± 0.1 relative gene expression in tumors from saline-treated mice compared to 1.78 ± 0.13 in tumors…
author: Soto Pantoja, David R
language: en_US
keywords: Angiotensin
date published: 2009-03-19T14:34:18Z
date modified: 2026-07-27T22:01:07Z
provider: Wake Forest University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Wake Forest University

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property ID: Handle
value: http://hdl.handle.net/10339/14863