Transcription factor Nkx-2.5 induces sodium/iodide symporter gene expression and participates in retinoic acid- and lactation-induced transcription in mammary cells

Monica Dentice, Cristina Luongo, Antonia Elefante, Romina Romino, Raffaele Ambrosio, Mario Vitale, Guido Rossi, Gianfranco Fenzi, Domenico Salvatore

Research output: Contribution to journalArticle

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Abstract

The sodium/iodide symporter (NIS) is a plasma membrane protein that mediates active iodide transport in thyroid and mammary cells. It is a prerequisite for radioiodide treatment of thyroid cancer and a promising diagnostic and therapeutic tool for breast cancer. We investigated the molecular mechanisms governing NIS expression in mammary cells. Here we report that Nkx-2.5, a cardiac homeobox transcription factor that is also expressed in the thyroid primordium, is a potent inducer of the NIS promoter. By binding to two specific promoter sites (N2 and W), Nkx-2.5 induced the rNIS promoter (about 50-fold over the basal level). Interestingly, coincident with NIS expression, Nkx-2.5 mRNA and protein were present in lactating, but not virgin, mammary glands in two human breast cancer samples and in all-trans retinoic acid (tRA)-stimulated MCF-7 breast cancer cells. A cotransfected dominant-negative Nkx-2.5 mutant abolished tRA-induced endogenous NIS induction, which shows that Nkx-2.5 activity is critical for this process. Remarkably, in MCF-7 cells, Nkx-2.5 overexpression alone was sufficient to induce NIS and iodide uptake. In conclusion, Nkx-2.5 is a novel relevant transcriptional regulator of mammary NIS and could thus be exploited to manipulate NIS expression in breast cancer treatment strategies.

Original languageEnglish
Pages (from-to)7863-7877
Number of pages15
JournalMolecular and Cellular Biology
Volume24
Issue number18
DOIs
Publication statusPublished - Sep 2004

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Tretinoin
Lactation
Breast
Breast Neoplasms
Gene Expression
Iodides
Thyroid Gland
Active Biological Transport
Homeobox Genes
MCF-7 Cells
Human Mammary Glands
Thyroid Neoplasms
Blood Proteins
Membrane Proteins
Transcription Factors
Cell Membrane
Messenger RNA
Homeobox Protein Nkx-2.5
sodium-iodide symporter
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Transcription factor Nkx-2.5 induces sodium/iodide symporter gene expression and participates in retinoic acid- and lactation-induced transcription in mammary cells. / Dentice, Monica; Luongo, Cristina; Elefante, Antonia; Romino, Romina; Ambrosio, Raffaele; Vitale, Mario; Rossi, Guido; Fenzi, Gianfranco; Salvatore, Domenico.

In: Molecular and Cellular Biology, Vol. 24, No. 18, 09.2004, p. 7863-7877.

Research output: Contribution to journalArticle

Dentice, Monica ; Luongo, Cristina ; Elefante, Antonia ; Romino, Romina ; Ambrosio, Raffaele ; Vitale, Mario ; Rossi, Guido ; Fenzi, Gianfranco ; Salvatore, Domenico. / Transcription factor Nkx-2.5 induces sodium/iodide symporter gene expression and participates in retinoic acid- and lactation-induced transcription in mammary cells. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 18. pp. 7863-7877.
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