Pre-B Lymphocyte Protein 3 (VPREB3) Expression in the Adrenal Cortex: Precedent for non-Immunological Roles in Normal an
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Pre-B Lymphocyte Protein 3 (VPREB3) Expression in the Adrenal Cortex: Precedent for non-Immunological Roles in Normal and Neoplastic Human Tissues Saulo J. A. Felizola 1 & Koshin Katsu 1 & Kazue Ise 1 & Yasuhiro Nakamura 1 & Yoichi Arai 2 & Fumitoshi Satoh 3 & Hironobu Sasano 1
Published online: 10 April 2015 # Springer Science+Business Media New York 2015
Abstract The pre-B lymphocyte protein 3 (VPREB3) is expressed during B cell differentiation and in subsets of mature B lymphocytes and is mainly found in bone marrow and lymphoid tissue germinative centers. So far, its function in B cells remains to be clarified. The messenger RNA (mRNA) of VPREB3 was previously detected in aldosterone-producing adenomas (APA); however, further information about this protein in human adrenocortical cells and tissues is currently unavailable. Therefore, in the present study, we, for the first time, investigate the protein expression of VPREB3 in human adrenocortical tissues. In addition, we approach the previously suggested similarities in expression patterns of aldosteroneproducing cells and Purkinje neurons. Immunohistochemical analysis of VPREB3 was performed in 13 nonpathological adrenals (NA), 6 adrenal glands with idiopathic hyperaldosteronism (IHA), 18 APA, 5 cortisol-producing adenomas (CPA), and 5 nonpathological human cerebellum specimens. The mRNA levels of VPREB3, steroidogenic enzymes, and other aldosterone biosynthesis markers were detected in 53 APA samples using real-time RT-PCR (qPCR) and compared to the clinical data of APA patients. In our
* Saulo J. A. Felizola [email protected] 1
Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
2
Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan
3
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Japan
results, the VPREB3 protein was diffusely detected in APA, partially or weakly detected in CPA, and immunolocalized in the zona glomerulosa of NA and IHA, as well as in the cytoplasm of cerebellar Purkinje cells. In APA, VPREB3 mRNA levels were significantly correlated to plasma aldosterone (P= 0.026; R = 0.30), KCNJ5 mutations (P = 0.0061; mutated 34:19 wild type), CYP11B2 (P
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