Abstract

BackgroundAquaporin3 (AQP3) and Aquaporin4 (AQP4) play a major role in transcellular and transepithelial water movement as water channel membrane proteins. Little is known of their expression and significance in human thyroid tissues. Thus, we examined the expression of AQP3 and AQP4 in normal, hyperplastic and neoplastic thyroid tissues in conjunction with human thyroid cancer cell lines.Methods and ResultsImmunohistochemical analyses demonstrated AQP3 in the cytoplasmic membrane of normal C cells, but not in follicular cells. In contrast, AQP4 was not found in C cells but was identified in normal follicular cells. AQP4 was positive in 92% of Graves’ disease thyroids and 97% of multinodular goiters, and we failed to demonstrate AQP3 in these hyperplastic tissues. In neoplastic thyroid lesions, we observed AQP3 in 91% of medullary thyroid carcinomas but in no other follicular cell tumors. AQP4 was demonstrated in 100% of follicular adenomas, 90% of follicular carcinomas, and 85% of papillary carcinomas, while it was negative in all medullary carcinomas and undifferentiated carcinomas. Reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed AQP3 mRNA expression only in medullary carcinomas and AQP4 mRNA expression in follicular cell-derived tumors except for undifferentiated carcinomas. In thyroid cancer cell lines, using RT-PCR and western blotting, AQP3 mRNA and protein were only identified in the TT cell line (human medullary carcinoma cell line) and AQP4 in the other cell lines. In addition, AQP3 mRNA expression was up-regulated by FBS and calcium administration in both a dose and time dependent manner in TT cells.ConclusionThe differential expressions of AQP3 and AQP4 may reflect the biological nature and/or function of normal, hyperplastic, and neoplastic thyroid cells and additionally may have value in determining differential diagnoses of thyroid tumors.

Highlights

  • Thyroid cancer is the most common malignancy of the endocrine organs, with incidence rates steadily increasing over the last several decades

  • The AQP family can be divided into 3 subgroups based on their primary sequences: aquaporins (AQP0, AQP1, AQP2, AQP4, AQP5, AQP6 and AQP8) that only transport water, aquaglyceroporins (AQP3, AQP7, AQP9 and AQP10) that are responsible for transporting water, glycerol and other small solutes [5], and superaquaporins belonging to a new subfamily (AQP11 and AQP12) [6,7]

  • We found AQP3 protein in the cytoplasmic membrane of normal thyroid C cells which were positive for calcitonin, while it was completely negative in follicular cells (Fig. 1A and B)

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Summary

Introduction

Thyroid cancer is the most common malignancy of the endocrine organs, with incidence rates steadily increasing over the last several decades. More than 95% of thyroid carcinomas are derived from follicular cells having a spectrum of differentiation from comparatively indolent carcinomas, including follicular thyroid carcinoma and papillary thyroid carcinoma, to poorly differentiated carcinoma and undifferentiated thyroid carcinoma Another thyroid carcinoma originating in the thyroid C cell is medullary carcinoma which occurs either sporadically or as part of the inherited, autosomal dominant, multiple endocrine neoplasia (MEN) type 2A and type 2B [1]. The Aquaporins (AQPs) are a family of small (,30 kDa/ monomer) membrane proteins that serve as water channel proteins that play a major role in transcellular and transepithelial water movement [2,3,4]. Aquaporin (AQP3) is a typical aquaglyceroporin transporting water, glycerol and urea that plays a major role in fluid homeostasis in normal tissues [8,9,10]. We examined the expression of AQP3 and AQP4 in normal, hyperplastic and neoplastic thyroid tissues in conjunction with human thyroid cancer cell lines

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