Expression of (pro)renin receptor in breast cancers and its effect on cancercell proliferation

Abstract

ABSTRACT(Pro)renin receptor ((P)RR) is a specific receptor for renin and prorenin. The aim of the present study is to clarify expression of (P)RR and pathophysiological roles of (P)RR in human breast carcinomas. (P)RR expression was studied in 69 clinical cases of breast carcinoma by immunohistochemistry. Effects of (P)RR on cell proliferation were examined in cultured human breast carcinoma cells using (P)RR specific small interference RNA. Immunohistochemistry showed that (P)RR immunoreactivity was detected in the breast carcinoma cells in 50 of 69 cases of breast carcinoma (72%). The analysis on association between (P)RR immunoreactivity and clinicopathological parameters showed that the number of (P)RR positive cases was significantly greater in Ki-67 (a cell proliferation marker) ≥ 10% group than in Ki-67 < 10% group (P = 0.02). (P)RR was expressed in 4 types of human breast carcinoma cell lines. (P)RR specific small interference RNA inhibited proliferation of both MCF-7 (ERα positive) and SK-BR-3 (ERα negative) cells. The present study has shown, for the first time, the expression of (P)RR in human breast carcinoma tissues and cultured breast carcinoma cell lines. These findings have raised the possibility that the blockade of the (P)RR signaling may be a novel therapeutic strategy against breast carcinomas.The renin-angiotensin system (RAS) plays important roles, not only in homeostatic regulation of blood pressure and water-electrolyte metabolism, but also in tumor biology including breast cancers. All the components of the RAS, including prorenin, renin, angiotensinogen (AGT), angiotensin I converting enzyme (ACE) and angiotensin receptors were localized in normal and cancerous breast tissues (28). Angiotensin II (Ang II) acts on the angiotensin II type 1 receptor (AT1R) to promote cell proliferation in breast cancer cells, via the protein kinase C/Ca 2+ / phosphoinositide 3-kinase pathways, and extracellular signal-related kinase (ERK) activation (32). Ang II promoted cell adhesion, invasion and metastasis of breast carcinoma by regulating the expression of integrins, vascular endothelial growth factor and matrix metalloproteinase-9 (22, 23). Clinicopathological study showed that AT1R expression in breast carcinoma tissues correlated with axillary lymph node metastasis (2). (Pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, consists of 350 amino acids

Microphthalmia‐associated transcription factor is expressed in projection neurons of the mouse olfactory bulb

“…After washing, the immune complex on the blots was detected using Immobilon ® Western (Millipore) and LAS 4000 (Fuji Film, Tokyo, Japan) (Ohba et al . ).…”

“…Secondary antibodies were diluted in Can Get Signal â Immunoreaction Enhancer Solution or PBS, which contained 0.5% BSA, and dilution ratio of secondary antibodies was 1:20 000. After washing, the immune complex on the blots was detected using Immobilon â Western (Millipore) and LAS 4000 (Fuji Film, Tokyo, Japan) (Ohba et al 2014).…”

Soluble (Pro)renin Receptor and Obstructive Sleep Apnea Syndrome: Oxidative Stress in Brain?

“…(P)RR was expressed in various types of tumor cells, such as aldosterone-secreting adenomas [30], breast cancers [31] and pancreatic ductal adenocarcinomas [32]. (P)RR may be related to the proliferation of tumor cells via ERK 1/2 signaling and/or the Wnt/β-catenin pathway.…”

Ubiquitous expression and multiple functions of biologically active peptides

“…Expression levels of (P)RR were elevated in aldosterone-secreting adenomas when compared with other types of adrenal adenomas and normal adrenal glands [99]. The suppression of (P)RR expression by (P)RR specific siRNA resulted in decrease proliferation of cultured breast cancer cells [62], suggesting that the (P)RR-mediated signaling stimulates proliferation of breast cancer cells.…”

“…For example, expression of (P)RR has been shown in neurons [81], anterior pituitary cells [81,91], adrenal cortex and medulla [99], erythroblastic cells [29], lymphocytes and monocytes [54]. Moreover, (P)RR is expressed in adrenal tumors [99] and breast cancers [62]. Expression levels of (P)RR were elevated in aldosterone-secreting adenomas when compared with other types of adrenal adenomas and normal adrenal glands [99].…”