Angiotensin-(1-7): A Peptide Hormone Inhibitor for the Treatment of Breast Cancer Targeting the Tumor Microenvironment
type: CreativeWork
description: In 2009, 192,000 new cases of breast cancer were diagnosed in the United States and over 40,000 American women died from breast cancer, emphasizing the severity of the breast cancer epidemic. Recent advances in molecular profiling of breast tumors have identified three clinically-relevant subcategories of breast cancer: estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) amplified, and triple negative (lacking the ER, the progesterone receptor (PR), and with normal expression of HER2) breast cancers. ER positive breast cancer is the most prevalent type of breast cancer accounting for over 70% of breast cancer cases while HER2-amplified breast cancer comprises an additional 20-25% of breast cancer cases. Drugs targeting estrogen biosynthesis, estrogen signaling, or HER2 amplification were developed and used for the treatment of breast cancer; however, drug resistance and adverse side effects have limited their use, emphasizing the need for new targeted drugs to treat breast cancer. The purpose of the studies described in this dissertation was to determine whether angiotensin-(1-7) [Ang-(1-7)], an endogenous seven amino-acid peptide hormone of the renin-angiotensin system, inhibits the growth of HER2-amplified and ER-positive orthotopic breast tumors and to identify the molecular mechanisms for the Ang-(1-7)-mediated reduction in tumor growth. BT-474, which express the ER receptor and over-express HER2, and ZR-75-1 ER positive cells were injected into a mammary fat pad of athymic mice. Tumors were allowed to grow to a uniform size, 200 mm3 and 100 mm3 for BT-474 and ZR-75-1, respectively, followed by treatment with Ang-(1-7) or saline for 18 days, to determine the effect of the drug on tumor growth. Ang-(1-7) administration reduced BT-474 and ZR-75-1 tumor volume by 68.2% and 77.0%, and tumor weight by 38.9% and 50%, respectively, indicating that the heptapeptide inhibits breast tumor growth. The Ang-(1-7)-mediated reduction in tumor growt…
abstract: In 2009, 192,000 new cases of breast cancer were diagnosed in the United States and over 40,000 American women died from breast cancer, emphasizing the severity of the breast cancer epidemic. Recent advances in molecular profiling of breast tumors have identified three clinically-relevant subcategories of breast cancer: estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) amplified, and triple negative (lacking the ER, the progesterone receptor (PR), and with normal expression of HER2) breast cancers. ER positive breast cancer is the most prevalent type of breast cancer accounting for over 70% of breast cancer cases while HER2-amplified breast cancer comprises an additional 20-25% of breast cancer cases. Drugs targeting estrogen biosynthesis, estrogen signaling, or HER2 amplification were developed and used for the treatment of breast cancer; however, drug resistance and adverse side effects have limited their use, emphasizing the need for new targeted drugs to treat breast cancer. The purpose of the studies described in this dissertation was to determine whether angiotensin-(1-7) [Ang-(1-7)], an endogenous seven amino-acid peptide hormone of the renin-angiotensin system, inhibits the growth of HER2-amplified and ER-positive orthotopic breast tumors and to identify the molecular mechanisms for the Ang-(1-7)-mediated reduction in tumor growth. BT-474, which express the ER receptor and over-express HER2, and ZR-75-1 ER positive cells were injected into a mammary fat pad of athymic mice. Tumors were allowed to grow to a uniform size, 200 mm3 and 100 mm3 for BT-474 and ZR-75-1, respectively, followed by treatment with Ang-(1-7) or saline for 18 days, to determine the effect of the drug on tumor growth. Ang-(1-7) administration reduced BT-474 and ZR-75-1 tumor volume by 68.2% and 77.0%, and tumor weight by 38.9% and 50%, respectively, indicating that the heptapeptide inhibits breast tumor growth. The Ang-(1-7)-mediated reduction in tumor growt…
author: Cook, Katherine
language: en_US
keywords: Cancer
date published: 2010-05-05T20:50:27Z
date modified: 2026-07-27T22:01:01Z
provider: Wake Forest University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Wake Forest University

PropertyValue
property ID: Handle
value: http://hdl.handle.net/10339/14833