Role of pro renin receptor in Ang II-mediated EGF receptor transactivation

Shibayama, Yuki; Hitomi, Hirofumi; Nakano, Daisuke; Kobori, Hiroyuki; Mori, Hirohito; Deguchi, Kazushi; Masaki, Tsutomu; Ichihara, Atsuhiro; Nishiyama, Akira

doi:10.2741/e650

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…Protein extraction and measurement of protein concentrations were performed, as previously described 43 . Total protein extracts (30 μg) were electrophoretically separated using 10% SDS-polyacrylamide gels and transferred onto nitrocellulose membranes.…”

Section: Methodsmentioning

confidence: 99%

(Pro)renin receptor is crucial for Wnt/β-catenin-dependent genesis of pancreatic ductal adenocarcinoma

Shibayama

Fujimori

Nguyen

et al. 2015

Sci Rep

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Although Wnt/β-catenin signaling is known to be aberrantly activated in PDAC, mutations of CTNNB1, APC or other pathway components are rare in this tumor type, suggesting alternative mechanisms for Wnt/β-catenin activation. Recent studies have implicated the (pro)renin receptor ((P)RR) is related to the Wnt/β-catenin signaling pathway. We therefore investigated the possible role of (P)RR in pancreatic carcinogenesis. Plasma s(P)RR levels were significantly (P < 0.0001) higher in patients with PDAC than in healthy matched controls. We also identified aberrant expression of (P)RR in premalignant PanIN and PDAC lesions and all the PDAC cell lines examined. Inhibiting (P)RR with an siRNA attenuated activation of Wnt/β-catenin signaling pathway and reduced the proliferative ability of PDAC cells in vitro and the growth of engrafted tumors in vivo. Loss of (P)RR induced apoptosis of human PDAC cells. This is the first demonstration that (P)RR may be profoundly involved in ductal tumorigenesis in the pancreas.

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Section: Methodsmentioning

confidence: 99%

(Pro)renin receptor is crucial for Wnt/β-catenin-dependent genesis of pancreatic ductal adenocarcinoma

Shibayama

Fujimori

Nguyen

et al. 2015

Sci Rep

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“…Antiproliferative Effects of (P)RR Antibodies on PDAC Cells AACRJournals.org Mol Cancer Ther; 19(9) September 2020 concentrations were measured as reported previously (22). Lysate samples were separated by 10% SDS-PAGE and proteins were transferred to nitrocellulose membranes.…”

Section: Western Blot Analysismentioning

confidence: 99%

Antiproliferative Effects of Monoclonal Antibodies against (Pro)Renin Receptor in Pancreatic Ductal Adenocarcinoma

Rahman

Matsuyama

Ebihara

et al. 2020

Molecular Cancer Therapeutics

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We previously reported that silencing of the PRR gene, which encodes the (pro)renin receptor [(P)RR], significantly reduced Wnt/b-catenin-dependent development of pancreatic ductal adenocarcinoma (PDAC). Here, we examined the effects of a panel of blocking mAbs directed against the (P)RR extracellular domain on proliferation of the human PDAC cell lines PK-1 and PANC-1 in vitro and in vivo. We observed that four rat anti-(P) RR mAbs induced accumulation of cells in the G 0 -G 1 -phase of the cell cycle and significantly reduced proliferation in vitro concomitant with an attenuation of Wnt/b-catenin signaling. Systemic administration of the anti-(P)RR mAbs to nude mice bearing subcutaneous PK-1 xenografts significantly decreased tumor expression of active b-catenin and the proliferation marker Ki-67, and reduced tumor growth. In contrast, treatment with the handle region peptide of (pro)renin did not inhibit tumor growth in vitro or in vivo, indicating that the effects of the anti-(P)RR mAbs were independent of the reninangiotensin system. These data indicate that mAbs against human (P)RR can suppress PDAC cell proliferation by hindering activation of the Wnt/b-catenin signaling pathway. Thus, mAb-mediated (P)RR blockade could be an attractive therapeutic strategy for PDAC.

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“…[5][6][7][8] PRR can be activated by either renin or prorenin; 9 however, prorenin appears to be the most relevant agonist since its plasma concentrations are approximately tenfold higher than those of renin and the binding affinity is threefold higher than renin. 10,11 The activation of PRR has been shown to drive cell cycle progression, DNA synthesis, ERK1(p44) and ERK2(p42) phosphorylation, [12][13][14] and p38 MAP kinase/ HSP27 activation, 15 all events associated with cell proliferation. Moreover, we have recently provided evidence that prorenin, through the activation of PRR, induces SMC migration.…”

Section: Introductionmentioning

confidence: 99%