Regulation of iodide uptake and sodium/iodide symporter expression in the mcf-7 human breast cancer cell line.
Sodium/iodide symporter (NIS) expression has recently been described in human breast cancer, with emphasis on its potential exploitation for the treatment of these tumors with radioiodine. In this study, we analyzed the regulation of NIS expression and function in the MCF-7 human breast cancer cell line. Cell exposure to insulin, IGF-I, IGF-II, or prolactin induced significant increases in 125I uptake and the expression of both NIS mRNA and NIS protein. The latter increases were evident after 6 and 12 h of hormonal stimulation, respectively. In immunocytochemistry studies, NIS was detected mainly in the plasma membrane of MCF-7 cells. A low but significant increase in iodide uptake was produced by treatment with activators of the adenylyl cyclase (cAMP) or protein kinase C pathways. Our study demonstrates that: 1) MCF-7 breast cancer cells are capable of active iodide transport that can be stimulated by insulin, IGF-I, IGF-II, or prolactin; 2) both NIS transcript and protein are expressed in these cells, and this expression is also hormonally stimulated; and 3) MCF-7 iodide transport and NIS expression may be influenced by the activation of cAMP or protein kinase C-dependent signaling. These findings increase our understanding of the molecular mechanisms that regulate NIS expression in breast cancer cells, information that is fundamental for future research aimed at the development of targeted radioiodide treatment for this type of cancer.
Arturi
Franco
F
Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro, "Magna Graecia," 88100 Catanzaro, Italy.
Ferretti
Elisabetta
E
Presta
Ivan
I
Mattei
Tiziana
T
Scipioni
Angela
A
Scarpelli
Daniela
D
Bruno
Rocco
R
Lacroix
Ludovic
L
Tosi
Emanuele
E
Gulino
Alberto
A
Russo
Diego
D
Filetti
Sebastiano
S
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D027981:Symporters / Q000032:analysis / Q000235:genetics*; D000099209:Sodium-Iodide Symporters
D005576:Colforsin; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D007454:Iodides; D010121:Oxytocin; D011388:Prolactin; D027981:Symporters; D000099209:Sodium-Iodide Symporters