NIS mediates iodide uptake in the female reproductive tract and is a poor prognostic factor in ovarian cancer.
BACKGROUND
The sodium iodide symporter (NIS) mediates active transport of iodide into the thyroid and the lactating mammary glands and is highly expressed in thyroid and breast carcinomas. NIS is clinically very relevant because it allows the treatment with radioiodine of thyroid cancer patients.


OBJECTIVE
In this study we wanted to explore whether NIS is expressed in the ovary and in ovarian cancer.


METHODS
Methods included NIS and paired box 8 expression and function in ovarian cancer patients and rats by immunochemistry, immunoblot, RT-PCR, and iodide uptake.


RESULTS
Here we demonstrate for the first time that NIS is expressed in the ovary and fallopian tube and actively accumulates significant levels of radioiodide in vivo. In a large survey of menstruating women receiving radioiodide for medical purposes, 15% showed significant uptake in the normal reproductive tract. Ovarian NIS activity is influenced by the estrous cycle stage in rats, being up-regulated during peak levels of estrogens occurring immediately before the ovulation. We unveil that the regulatory mechanism underlying this phenomenon is based on the functional cooperation of estrogen receptor-α and paired box 8. We also show that NIS is highly expressed in ovarian cancer, predicting a poor prognosis in these patients.


CONCLUSIONS
These results provide the basis that will help minimize the impact of therapeutic doses of radioiodide on gonadal function. We also suggest that NIS is a new ovarian cancer marker, opening a door for the use of radioiodide in the diagnosis and treatment of ovarian cancer patients.
Instituto de Investigaciones Biomédicas (G.R.-E., S.G.L., M.A.E.-C., P.S.), Consejo Superior de Investigaciones Científicas (CSIC-UAM) 28029 Madrid, Spain; Servicio de Endocrinología y Nutrición (G.R-E.), Departamento de Anatomía Patologica (M.M., D.H.), and Servicio de Oncología Medica (A.R.), Hospital Universitario La Paz, IdPAZ, 28046, Madrid, Spain; and Unidad de Patología Mamaria (M.I.G.) and Unidad de Tumores Endocrinos (A.D.l.V.), Unidad Funcional de Investigación en Enfermedades Crónicas (UFIEC), Instituto de Salud Carlos III, 28220, Majadahonda, Madrid, Spain.
Garcilaso
G
Riesco-Eizaguirre
Suzana Garcia
SG
Leoni
Marta
M
Mendiola
Maria Angeles
MA
Estevez-Cebrero
Marta Ines
MI
Gallego
Andrés
A
Redondo
David
D
Hardisson
Pilar
P
Santisteban
Antonio
A
De la Vieja
D000328:Adult; D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D005836:Genitalia, Female / Q000378:metabolism* / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D007455:Iodine / Q000378:metabolism*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000502:physiology*; D000099209:Sodium-Iodide Symporters
D007455:Iodine; D027981:Symporters; D000099209:Sodium-Iodide Symporters