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The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

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dc.contributor.author Ryan, James en
dc.contributor.author Curran, Catherine E. en
dc.contributor.author Hennessy, Emer en
dc.contributor.author Newell, John en
dc.contributor.author Kerin, Michael J. en
dc.contributor.author Dwyer, Roisin M. en
dc.date.accessioned 2011-05-25T12:05:14Z en
dc.date.available 2011-05-25T12:05:14Z en
dc.date.issued 2011-01 en
dc.identifier.citation Ryan J, Curran CE, Hennessy E, Newell J, Morris JC, et al. (2011) The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue. PLoS ONE 6(1): e16023. doi:10.1371/journal.pone.0016023 en
dc.identifier.uri http://hdl.handle.net/10379/1932 en
dc.description.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 (RAR¿, RAR¿), oestrogen (ER¿), thyroid hormones (THR¿, THR¿), 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 ER¿ (r = 0.22, p<0.05) and RAR¿ (r = 0.29, p<0.005), with the strongest relationship observed between NIS and RAR¿ (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. en
dc.format application/pdf en
dc.language.iso en en
dc.subject Surgery en
dc.title The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue en
dc.type Article en
dc.local.publishedsource http://dx.crossref.org/10.1371/journal.pone.0016023 en
dc.description.peer-reviewed peer-reviewed en
dc.contributor.funder Cancer Research Ireland en
dc.contributor.funder HRB en
dc.contributor.funder National Breast Cancer Research Institute en

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