title: Systemic retinoic acid treatment induces sodium/iodide symporter expression and radioiodide uptake in mouse breast cancer models.
abstract: Lactating breast tissue and some breast cancers express the sodium/iodide symporter (NIS) and concentrate iodide. We recently demonstrated that all-trans retinoic acid (tRA) induces both NIS gene expression and iodide accumulation in vitro in well-differentiated human breast cancer cells (MCF-7). In the present study, we investigated the in vivo efficacy and specificity of tRA-stimulated iodide accumulation in mouse breast cancer models. Immunodeficient mice with MCF-7 xenograft tumors were treated with systemic tRA for 5 days. Iodide accumulation in the xenograft tumors was markedly increased, approximately 15-fold greater than levels without treatment, and the effects were tRA dose dependent. Iodide accumulation in other organs was not significantly influenced by tRA treatment. Significant induction of NIS mRNA and protein in the xenograft tumors was observed after tRA treatment. Iodide accumulation and NIS mRNA expression were also selectively induced in breast cancer tissues in transgenic mice expressing the oncogene, polyoma virus middle T antigen. These data demonstrate selective induction of functional NIS in breast cancer by tRA. Treatment with short-term systemic retinoic acid, followed by radioiodide administration, is a potential tool in the diagnosis and treatment of some differentiated breast cancer.
authors.affiliation: Molecular Endocrinology Laboratory, VA Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Kogai
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kanamoto
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Che
authors.forename: Katsumi
authors.initials: K
authors.lastname: Taki
authors.forename: Farhad
authors.initials: F
authors.lastname: Moatamed
authors.forename: James J
authors.initials: JJ
authors.lastname: Schultz
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Brent
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D051379:Mice; D016513:Mice, SCID; D011877:Radionuclide Imaging; D027981:Symporters / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014212:Tretinoin / Q000494:pharmacology*; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D014212:Tretinoin; D000099209:Sodium-Iodide Symporters