Garcilaso Riesco-Eizaguirre1, Suzana Garcia Leoni, Marta Mendiola, Maria Angeles Estevez-Cebrero, Marta Ines Gallego, Andrés Redondo, David Hardisson, Pilar Santisteban, Antonio De la Vieja. 1. 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.
Abstract
CONTEXT: 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/PATIENTS: 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.
CONTEXT: 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 cancerpatients. OBJECTIVE: In this study we wanted to explore whether NIS is expressed in the ovary and in ovarian cancer. METHODS/PATIENTS: Methods included NIS and paired box 8 expression and function in ovarian cancerpatients 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 cancerpatients.
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