The renin–angiotensin system in the breast and breast cancer

Abstract

Much evidence now suggests that angiotensin II has roles in normal functions of the breast that may be altered or attenuated in cancer. Both angiotensin type 1 (AT1) and type 2 (AT2) receptors are present particularly in the secretory epithelium. Additionally, all the elements of a tissue renin-angiotensin system, angiotensinogen, prorenin and angiotensin-converting enzyme (ACE), are also present and distributed in different cell types in a manner suggesting a close relationship with sites of angiotensin II activity. These findings are consistent with the concept that stromal elements and myoepithelium are instrumental in maintaining normal epithelial structure and function. In disease, this system becomes disrupted, particularly in invasive carcinoma. Both AT1 and AT2 receptors are present in tumours and may be up-regulated in some. Experimentally, angiotensin II, acting via the AT1 receptor, increases tumour cell proliferation and angiogenesis, both these are inhibited by blocking its production or function. Epidemiological evidence on the effect of expression levels of ACE or the distribution of ACE or AT1 receptor variants in many types of cancer gives indirect support to these concepts. It is possible that there is a case for the therapeutic use of high doses of ACE inhibitors and AT1 receptor blockers in breast cancer, as there may be for AT2 receptor agonists, though this awaits full investigation. Attention is drawn to the possibility of blocking specific AT1-mediated intracellular signalling pathways, for example by AT1-directed antibodies, which exploit the possibility that the extracellular N-terminus of the AT1 receptor may have previously unsuspected signalling roles.

The renin-angiotensin system meets the hallmarks of cancer

“…But others, such as the renin-angiotensin system (RAS), which is known for controlling the homeostasis of the organism and not for any apparent involvement in cancer, are now being added to the complex networks of carcinogenesis. 3 The RAS was first discovered and extensively studied in the physiological regulation of systemic arterial pressure and, therefore, in the pathogenesis of hypertension. 4 As a gatekeeper system, RAS is involved in more than one function.…”

Normolipidic Dietary Fat Modifies Circulating Renin–Angiotensin System–Regulating Aminopeptidase Activities in Rat With Breast Cancer

“…18,19 The 2 main bioactive peptides of the RAS, Ang II and its direct metabolite Ang III, exhibit the same affinity for type 1 and type 2 angiotensin receptors, 20,21 and it is known that AT1 and AT2 receptors are expressed in breast cancer. 8 In this work, the influence of dietary fat on aminopeptidase activities involved in RAS metabolism in NMU-induced breast cancer animals has been also analyzed. We observed that APA is increased in all the studied groups; therefore, this effect could be due to tumor rather than the diet.…”

“…5 Also, local RAS can participate in various pathological processes such as cancer. 6,7 It is known that Ang II regulates cell turnover by promoting both cell proliferation and programmed cell death through differential actions via the AT1 and AT2 receptors, 8 and also it is known that AT1 and AT2 receptors are expressed in breast cancer. However, Ang II is not the only element of RAS that participates in cancer.…”

Lack of association of angiotensin-converting enzyme insertion/deletion polymorphism with breast cancer: An update meta-analysis based on 10405 subjects

“…7,8 Previous studies indicated that ACE inhibitor could lower the breast cancer risk. 29 In recent years, more and more publications suggested that the ACE I/D polymorphism is related to breast cancer risk.…”