The sodium iodide Symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue

James Ryan, Catherine E. Curran, Emer Hennessy, John Newell, John C. Morris, Michael J. Kerin, Roisin M. Dwyer

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Introduction: The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Methods: Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. Results: The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log10 Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log10RQ, p<0.005) and malignant breast tissue (1.18(0.07) Log10RQ, p<0.05). Significant positive correlations were observed between human NIS and ERa (r = 0.22, p<0.05) and RARa (r = 0.29, p<0.005), with the strongest relationship observed between NIS and RARb (r = 0.38, p<0.0001). An inverse relationship between NIS and PI3K expression was also observed (r =-0.21, p<0.05). In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6-16 fold), while ATRA and Thyroxine combined caused the greatest increase (range 16-26 fold). Conclusion: Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones.

Original languageEnglish (US)
Article numbere16023
JournalPLoS One
Volume6
Issue number1
DOIs
StatePublished - 2011

Fingerprint

symporters
iodides
breasts
Breast
sodium
Tissue
Fibroadenoma
Thyroxine
retinoic acid
thyroxine
Estradiol
estradiol
Phosphatidylinositols
1-Phosphatidylinositol 4-Kinase
Tretinoin
Thyroid Hormones
phosphatidylinositol 3-kinase
thyroid hormones
Phosphotransferases
Retinoic Acid Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ryan, J., Curran, C. E., Hennessy, E., Newell, J., Morris, J. C., Kerin, M. J., & Dwyer, R. M. (2011). The sodium iodide Symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue. PLoS One, 6(1), [e16023]. https://doi.org/10.1371/journal.pone.0016023

The sodium iodide Symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue. / Ryan, James; Curran, Catherine E.; Hennessy, Emer; Newell, John; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M.

In: PLoS One, Vol. 6, No. 1, e16023, 2011.

Research output: Contribution to journalArticle

Ryan, J, Curran, CE, Hennessy, E, Newell, J, Morris, JC, Kerin, MJ & Dwyer, RM 2011, 'The sodium iodide Symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue', PLoS One, vol. 6, no. 1, e16023. https://doi.org/10.1371/journal.pone.0016023
Ryan, James ; Curran, Catherine E. ; Hennessy, Emer ; Newell, John ; Morris, John C. ; Kerin, Michael J. ; Dwyer, Roisin M. / The sodium iodide Symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue. In: PLoS One. 2011 ; Vol. 6, No. 1.
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