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

Shibayama Y, Fujimori T, Nguyen G, Hirose T, Totsune K, Ichihara A, Kitada K, Nakano D, Kobori H, Kohno M, Masaki T, Suzuki Y, Yachida S, Nishiyama A - Sci Rep (2015)

Bottom Line: Plasma s(P)RR levels were significantly (P < 0.0001) higher in patients with PDAC than in healthy matched controls.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.

ABSTRACT
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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Related in: MedlinePlus

Plasma s(P)RR levels in patients with PDAC and amounts in the conditioned medium of human PDAC cell lines.(a) Plasma s(P)RR levels in 20 patients with PDAC and 20 healthy matched controls. Data are mean ± SD values. The boxes encompass the twenty-fifth through seventy-fifth percentiles of results. The lines through the middle of each box represent the medians. The maximum and minimum values within 1.5 × interquartile range (IQR) are shown as whisker caps. Average values are indicated by dots in the boxes. (b) s(P)RR in conditioned medium was assayed for HPDE cells and six different PDAC cell lines. Consistent results were observed when three experiments were repeated. Loading control was determined by CBB staining.
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f1: Plasma s(P)RR levels in patients with PDAC and amounts in the conditioned medium of human PDAC cell lines.(a) Plasma s(P)RR levels in 20 patients with PDAC and 20 healthy matched controls. Data are mean ± SD values. The boxes encompass the twenty-fifth through seventy-fifth percentiles of results. The lines through the middle of each box represent the medians. The maximum and minimum values within 1.5 × interquartile range (IQR) are shown as whisker caps. Average values are indicated by dots in the boxes. (b) s(P)RR in conditioned medium was assayed for HPDE cells and six different PDAC cell lines. Consistent results were observed when three experiments were repeated. Loading control was determined by CBB staining.

Mentions: Fig. 1a shows plasma concentrations of s(P)RR in 20 patients with PDAC and 20 healthy controls. The information of age and gender of healthy control subjects was provided in supplementary Table S1. Supplementary Table S2 summarizes clinical characteristics of patients. Blood collection was performed during the same period in National Cancer Center, Tokyo Japan, and 20 potential controls were frequency-matched to the patients in eight age categories (50–54, 55–59, 60–64, 65–69, 70–74, 75–79, 80–84 and 85–89 years of age) and sex. As shown in Fig. 1a, plasma s(P)RR levels were significantly (P < 0.0001) higher in patients with PDAC (14.67 ± 3.64 ng/mL) than in healthy controls (8.45 ± 1.37 ng/mL).


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

Shibayama Y, Fujimori T, Nguyen G, Hirose T, Totsune K, Ichihara A, Kitada K, Nakano D, Kobori H, Kohno M, Masaki T, Suzuki Y, Yachida S, Nishiyama A - Sci Rep (2015)

Plasma s(P)RR levels in patients with PDAC and amounts in the conditioned medium of human PDAC cell lines.(a) Plasma s(P)RR levels in 20 patients with PDAC and 20 healthy matched controls. Data are mean ± SD values. The boxes encompass the twenty-fifth through seventy-fifth percentiles of results. The lines through the middle of each box represent the medians. The maximum and minimum values within 1.5 × interquartile range (IQR) are shown as whisker caps. Average values are indicated by dots in the boxes. (b) s(P)RR in conditioned medium was assayed for HPDE cells and six different PDAC cell lines. Consistent results were observed when three experiments were repeated. Loading control was determined by CBB staining.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352858&req=5

f1: Plasma s(P)RR levels in patients with PDAC and amounts in the conditioned medium of human PDAC cell lines.(a) Plasma s(P)RR levels in 20 patients with PDAC and 20 healthy matched controls. Data are mean ± SD values. The boxes encompass the twenty-fifth through seventy-fifth percentiles of results. The lines through the middle of each box represent the medians. The maximum and minimum values within 1.5 × interquartile range (IQR) are shown as whisker caps. Average values are indicated by dots in the boxes. (b) s(P)RR in conditioned medium was assayed for HPDE cells and six different PDAC cell lines. Consistent results were observed when three experiments were repeated. Loading control was determined by CBB staining.
Mentions: Fig. 1a shows plasma concentrations of s(P)RR in 20 patients with PDAC and 20 healthy controls. The information of age and gender of healthy control subjects was provided in supplementary Table S1. Supplementary Table S2 summarizes clinical characteristics of patients. Blood collection was performed during the same period in National Cancer Center, Tokyo Japan, and 20 potential controls were frequency-matched to the patients in eight age categories (50–54, 55–59, 60–64, 65–69, 70–74, 75–79, 80–84 and 85–89 years of age) and sex. As shown in Fig. 1a, plasma s(P)RR levels were significantly (P < 0.0001) higher in patients with PDAC (14.67 ± 3.64 ng/mL) than in healthy controls (8.45 ± 1.37 ng/mL).

Bottom Line: Plasma s(P)RR levels were significantly (P < 0.0001) higher in patients with PDAC than in healthy matched controls.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus