Retinoic acid induces sodium/iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line

The sodium/iodide symporter (NIS) stimulates iodide uptake in normal lactat ing breast, but is not known to be active in nonlactating breast or breast cancer. We studied NIS gene regulation and iodide uptake in MCF-7 cells, an estrogen receptor (ER)-positive human breast cancer cell line. All-trans r etinoic acid (tRA) treatment stimulated iodide uptake in a time- and dose-d ependent fashion up to approximate to 9.4-fold above baseline. Stimulation with selective retinoid compounds indicated that the induction of iodide up take was mediated by retinoic acid receptor. Treatment with tRA markedly st imulated NIS mRNA and immunoreactive protein ( approximate to 68 kDa). tRA stimulated NIS gene transcription approximate to 4-fold, as shown by nuclea r run-on assay. No induction of iodide uptake was observed with RA treatmen t of an ER-negative human breast cancer cell line, MDA-MB 231, or a normal human breast cell line, MCF-12A. The iodide efflux rate of tRA-treated MCF- 7 cells was slow (t(1/2) = 24 min), compared with that in FRTL-5 thyroid ce lls (t(1/2) = 3.9 min), favoring iodide retention in MCF-7 cells. An in vit ro clonogenic assay demonstrated selective cytotoxicity with I-131 after tR A stimulation of MCF-7 cells. tRA up-regulates NIS gene expression and iodi de uptake in an ER-positive breast cancer cell line. Stimulation of radioio dide uptake after systemic retinoid treatment may be useful for diagnosis a nd treatment of some differentiated breast cancers.