2024-03-28T13:30:03Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/248142016-02-16T07:38:39Zcom_10261_22com_10261_1col_10261_275
Hydrocortisone and Purinergic Signaling Stimulate Sodium/Iodide Symporter (NIS)-Mediated Iodide Transport in Breast Cancer Cells
Dohán, Orsolya
Vieja, Antonio de la
Carrasco, Nancy
18 pages, 6 figures.
The sodium/iodide symporter (NIS) mediates a remarkably effective targeted radioiodide therapy in thyroid cancer; this approach is an emerging candidate for treating other cancers that express NIS, whether endogenously or by exogenous gene transfer. Thus far, the only extrathyroidal malignancy known to express functional NIS endogenously is breast cancer. Therapeutic efficacy in thyroid cancer requires that radioiodide uptake be maximized in tumor cells by manipulating well-known regulatory factors of NIS expression in thyroid cells, such as TSH, which stimulates NIS expression via cAMP. Similarly, therapeutic efficacy in breast cancer will likely depend on manipulating NIS regulation in mammary cells, which differs from that in the thyroid. Human breast adenocarcinoma MCF-7 cells modestly express endogenous NIS when treated with all-trans-retinoic acid (tRa). We report here that hydrocortisone and ATP each markedly stimulates tRa-induced NIS protein expression and plasma membrane targeting in MCF-7 cells, leading to at least a 100% increase in iodide uptake. Surprisingly, the adenyl cyclase activator forskolin, which promotes NIS expression in thyroid cells, markedly decreases tRa-induced NIS protein expression in MCF-7 cells. Isobutylmethylxanthine increases tRa-induced NIS expression in MCF-7 cells, probably through a purinergic signaling system independent of isobutylmethylxanthine’s action as a phosphodiesterase inhibitor. We also observed that neither iodide, which at high concentrations down-regulates NIS in the thyroid, nor cAMP has a significant effect on NIS expression in MCF-7 cells. Our findings may open new strategies for breast-selective pharmacological modulation of functional NIS expression, thus improving the feasibility of using radioiodide to effectively treat breast cancer.
This work was supported by National Institutes of Health
Grant CA098390 (to N.C.). O.D. was supported, in part, by a
postdoctoral award from the Department of Defense
(DAMD17-0010127).
Peer reviewed
2010-05-28T10:11:37Z
2010-05-28T10:11:37Z
2006-05
artículo
http://purl.org/coar/resource_type/c_6501
Molecular Endocrinology 20(5): 1121-1137 (2006)
0888-8809
http://hdl.handle.net/10261/24814
10.1210/me.2005-0376
en
http://dx.doi.org/10.1210/me.2005-0376
open
1869287 bytes
application/pdf
Endocrine Society