Expression of (pro)renin receptor in breast cancers and its effect on cancercell proliferation.
(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.
Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi,Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
Koji
K
Ohba
Takashi
T
Suzuki
Hiroshi
H
Nishiyama
Kiriko
K
Kaneko
Takuo
T
Hirose
Kazuhito
K
Totsune
Hironobu
H
Sasano
Kazuhiro
K
Takahashi
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D018942:Macrolides / Q000494:pharmacology; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000378:metabolism / Q000494:pharmacology; D012307:Risk Factors; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D000093342:Prorenin Receptor
D000804:Angiotensin II; D014408:Biomarkers, Tumor; D018942:Macrolides; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor; C040929:bafilomycin A1