Department of Human Pathology, University of Yamanashi Interdisciplinary Graduate School of Medicine and Engineering, Yamanashi, Japan.
PLoS One. 2012;7(7):e40770. doi: 10.1371/journal.pone.0040770. Epub 2012 Jul 10.
Aquaporin3 (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.
Immunohistochemical 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.
The 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.
水通道蛋白 3（AQP3）和水通道蛋白 4（AQP4）作为水通道膜蛋白，在细胞间和上皮细胞间的水移动中起主要作用。它们在人类甲状腺组织中的表达和意义知之甚少。因此，我们结合人甲状腺癌细胞系，研究了 AQP3 和 AQP4 在正常、增生和肿瘤性甲状腺组织中的表达。
免疫组化分析显示 AQP3 存在于正常 C 细胞的细胞质膜中，但不存在于滤泡细胞中。相反，AQP4 不存在于 C 细胞中，但存在于正常滤泡细胞中。AQP4 在 Graves 病甲状腺的 92%和多结节性甲状腺肿的 97%中呈阳性，我们未能在这些增生性组织中检测到 AQP3。在肿瘤性甲状腺病变中，我们观察到 91%的甲状腺髓样癌中存在 AQP3，但在其他滤泡细胞肿瘤中不存在。AQP4 在 100%的滤泡性腺瘤、90%的滤泡状癌和 85%的乳头状癌中呈阳性，而在所有甲状腺髓样癌和未分化癌中均呈阴性。逆转录聚合酶链反应（RT-PCR）分析显示，只有在甲状腺髓样癌中存在 AQP3mRNA 表达，在除未分化癌以外的滤泡细胞来源肿瘤中存在 AQP4mRNA 表达。在甲状腺癌细胞系中，通过 RT-PCR 和 Western blot 分析，仅在 TT 细胞系（人甲状腺髓样癌细胞系）中鉴定到 AQP3mRNA 和蛋白，在其他细胞系中鉴定到 AQP4。此外，AQP3mRNA 表达在 TT 细胞中呈剂量和时间依赖性上调，由 FBS 和钙处理引起。
AQP3 和 AQP4 的差异表达可能反映了正常、增生和肿瘤性甲状腺细胞的生物学性质和/或功能，此外，对于确定甲状腺肿瘤的鉴别诊断可能具有价值。
