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 (Mitf) is a key regulator for differentiation of the neural crest‐derived melanocytes. Mitf consists of multiple isoforms, including melanocyte‐specific Mitf‐M and widely expressed Mitf‐A and Mitf‐H. Mitf mRNAs are also expressed in the brain, although the identity of Mitf‐expressing cells remains unknown. We therefore aimed to identify Mitf‐expressing cells in the brain. By the immunohistochemical analysis, we detected Mitf‐expressing cells only in the olfactory bulb of the C57BL/6 mouse. The Mitf‐expressing cells were then identified as projection neurons, mitral cells and tufted cells, both of which receive the signal from the olfactory neurons and transmit the information to the olfactory cortex. Real‐time RT‐PCR analysis showed the expression level of Mitf‐M mRNA was comparable to the expression levels of Mitf‐A and Mitf‐H mRNAs in the olfactory bulb. We then analyzed Mitf‐expressing neurons in the olfactory bulb of the homozygous black‐eyed white (Mitfmi‐bw) mouse that is characterized by the lack of melanocytes. Mitf was expressed in mitral cells and tufted cells in the olfactory bulb of the Mitfmi‐bw mouse, thereby excluding the contribution of melanocytes to the detected expression of Mitf‐M. In conclusion, Mitf, including Mitf‐M, is expressed in mitral cells and tufted cells of the olfactory bulb.
Melanocytes develop from the vertebrate embryo-specific neural crest, migrate, and localize in various organs, including not only the skin but also several extracutaneous locations such as the heart, inner ear and choroid. Little is known about the functions of extracutaneous melanocytes except for cochlear melanocytes, which are essential for hearing ability. In this study, we focused on the structure of the choroid, in which melanocytes are abundant around the well-developed blood vascular system. By comparing structural differences in the choroid of wild-type and melanocyte-deficient
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