Targeting sodium/iodide symporter gene expression for estrogen-regulated imaging and therapy in breast cancer.
Expression of the sodium iodide symporter (hNIS) has been detected in breast cancer tissue, but frequently, not at the levels necessary to mediate (131)I accumulation. Transducing the hNIS gene into breast cancer cells with adenovirus could be a tractable strategy to render breast cancer susceptible to radioiodide therapy. We constructed the replication-incompetent virus, AdSERE, in which an estrogen-responsive promoter directs the expression of hNIS. In vitro, we demonstrate that AdSERE mediates hNIS expression and iodide uptake in ER+ breast cancer cells. In vivo, we show that AdSERE-infected ER+ tumors can be imaged due to tracer accumulation; in addition, AdSERE in combination with therapeutic doses of (131)I suppresses tumor growth.
Montiel-Equihua
C A
CA
Centre for Molecular Oncology, Institute of Cancer and CR-UK Clinical Centre, Barts and The London, School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
Martín-Duque
P
P
de la Vieja
A
A
Quintanilla
M
M
Burnet
J
J
Vassaux
G
G
Lemoine
N R
NR
D000256:Adenoviridae; D000818:Animals; D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D005455:Fluorescent Antibody Technique; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011878:Radiotherapy / Q000379:methods*; D011960:Receptors, Estrogen / Q000378:metabolism*; D027981:Symporters / Q000235:genetics* / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D027981:Symporters; D001616:beta-Galactosidase; D000099209:Sodium-Iodide Symporters