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The mammary gland iodide transporter is expressed during lactation and in breast cancer

Abstract

The sodium/iodide symporter mediates active iodide transport in both healthy and cancerous thyroid tissue. By exploiting this activity, radioiodide has been used for decades with considerable success in the detection and treatment of thyroid cancer. Here we show that a specialized form of the sodium/iodide symporter in the mammary gland mediates active iodide transport in healthy lactating (but not in nonlactating) mammary gland and in mammary tumors. In addition to characterizing the hormonal regulation of the mammary gland sodium/iodide symporter, we demonstrate by scintigraphy that mammary adenocarcinomas in transgenic mice bearing Ras or Neu oncogenes actively accumulate iodide by this symporter in vivo. Moreover, more than 80% of the human breast cancer samples we analyzed by immunohistochemistry expressed the symporter, compared with none of the normal (nonlactating) samples from reductive mammoplasties. These results indicate that the mammary gland sodium/iodide symporter may be an essential breast cancer marker and that radioiodide should be studied as a possible option in the diagnosis and treatment of breast cancer.

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Figure 1: TPT accumulation and NIS expression in rat stomach and lactating mammary gland.
Figure 2: mgNIS expression at different physiological stages in murine mammary gland.
Figure 3: Effect of oxytocin on functional mgNIS expression in nubile mice.
Figure 4: Analysis of mammary adenocarcinomas in MMTV–Ras and MMTV–Neu transgenic mice.
Figure 5: NIS expression in human salivary gland and breast tissues.

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Acknowledgements

We thank A. De la Vieja and C. Riedel for computer assistance, G. Orr for advice and T. Ciao and G. Dai for help with animal experiments. We also thank L. M. Amzel, T. Graf, and the members of the Carrasco laboratory for reviewing the manuscript. O.L. was supported by the National Institutes of Health Hepatology Research Training Grant DK-07218. R.G.P. is a recipient of the Irma T. Hirschl award. This work was supported in part by R29CA70897 and RO1CA75503 (to R.G.P.). Work at the Albert Einstein College of Medicine was supported by Cancer Center Core National Institutes of Health grant 5-P30-CA13330-26. This project was also supported by the National Institutes of Health DK-41544, the Susan G. Komen Breast Cancer Foundation, the American Cancer Society BE-79422, and the Irma T. Hirschl award (N.C.).

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Correspondence to Nancy Carrasco.

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Tazebay, U., Wapnir, I., Levy, O. et al. The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med 6, 871–878 (2000). https://doi.org/10.1038/78630

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