Differential expression of aquaporins and its diagnostic utility in thyroid cancer

PLoS One. 2012;7(7):e40770. doi: 10.1371/journal.pone.0040770. Epub 2012 Jul 10.


Background: 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.

Methods and results: 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.

Conclusion: 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.

MeSH terms

  • Aquaporin 3 / genetics*
  • Aquaporin 3 / metabolism
  • Aquaporin 4 / genetics*
  • Aquaporin 4 / metabolism
  • Calcium / pharmacology
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Humans
  • Hyperplasia
  • Immunohistochemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serum / metabolism
  • Thyroid Gland / drug effects
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology


  • AQP3 protein, human
  • AQP4 protein, human
  • Aquaporin 4
  • RNA, Messenger
  • Aquaporin 3
  • Calcium