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Endocr Relat Cancer. 2019 Sep 1. pii: ERC-19-0314.R1. doi: 10.1530/ERC-19-0314. [Epub ahead of print]

Mechanisms linking the renin-angiotensin system, obesity, and breast cancer.

Author information

1
F Rasha, Nutritional Sciences, Texas Tech University, Lubbock, 79409, United States.
2
L Ramalingam, Nutritional Sciences, Texas Tech University, Lubbock, United States.
3
L Gollahon, Biological Sciences, Texas Tech University, Lubbock, United States.
4
R Rahman, Surgery, Medicine, Texas Tech University Health Sciences Center, Lubbock, United States.
5
S Rahman, Nutritional Sciences, Texas Tech University, Lubbock, United States.
6
K Menikdiwela, Nutritional Sciences, Texas Tech University, Lubbock, United States.
7
N Moustaid-Moussa, Nutritional Sciences, Texas Tech University, Lubbock, 79409, United States.

Abstract

Obesity is a complex disease and a global epidemic. It is a risk factor for other chronic diseases including breast cancer, especially in women after menopause. Diverse etiologies underlie the relationship between obesity and breast cancer. Adipose tissue is in part responsible for these interactions. In obesity, adipose tissue undergoes several metabolic dysregulations resulting in secretion of many proinflammatory cytokines, growth factors, and hormones which in turn, can promote tumor microenvironment (TME) formation and cancer progression within the breast tissue. Angiotensin II (Ang II) is a well-known hypertensive hormone produced systemically and locally by the renin-angiotensin system (RAS). Activation of this system in obesity is a potential contributor to local and systemic inflammation in breast adipose tissue. Ang II actions are primarily mediated through binding to its two receptors, type 1 (AT1R) and type 2 (AT2R). RAS inhibitors include angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) which are currently prescribed as safe anti-hypertensive therapies. Recent studies have explored potential use of ACE-I and ARBs in breast cancer patients as anti-tumor agents. Therefore, it is vital to understand the role of RAS in breast cancer, and identify mechanisms of Ang II and RAS inhibitors in the TME and in obesity and breast cancer crosstalk. In this review, we performed a detailed analysis and discussed mechanisms of Ang II-AT1R interactions in breast cancer with emphasis on obesity-associated breast cancer. We further summarized recent in vitro, in vivo and human studies that used ACE-I/ARB interventions to improve breast cancer outcomes.

PMID:
31525726
DOI:
10.1530/ERC-19-0314

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