Signaling through 3',5'-cyclic adenosine monophosphate and phosphoinositide-3 kinase induces sodium/iodide symporter expression in breast cancer.
The sodium/iodide symporter (NIS) is a membrane transport glycoprotein normally expressed in the thyroid gland and lactating mammary gland. NIS is a target for radioiodide imaging and therapeutic ablation of thyroid carcinomas and has the potential for similar use in breast cancer treatment. To facilitate NIS-mediated radionuclide therapy, it is necessary to identify signaling pathways that lead to increased NIS expression and function in breast cancer. We examined NIS expression in mammary tumors of 14 genetically engineered mouse models to identify genetic manipulations associated with NIS induction. The cAMP and phosphoinositide-3 kinase (PI3K) signaling pathways are associated with NIS up-regulation. We showed that activation of PI3K alone is sufficient to increase NIS expression and radioiodide uptake in MCF-7 human breast cancer cells, whereas cAMP stimulation increases NIS promoter activity and NIS mRNA levels but is not sufficient to increase radioiodide uptake. This study is the first to demonstrate that NIS expression is induced by cAMP and/or PI3K in breast cancer both in vivo and in vitro.
Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA.
Katherine A B
KA
Knostman
Je-Yoel
JY
Cho
Kwon-Yul
KY
Ryu
Xiaoqin
X
Lin
James A
JA
McCubrey
Timothy
T
Hla
Catherine H
CH
Liu
Emma
E
Di Carlo
Ruth
R
Keri
Ming
M
Zhang
Dae Y
DY
Hwang
William C
WC
Kisseberth
Charles C
CC
Capen
Sissy M
SM
Jhiang
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
D000242:Cyclic AMP; D007457:Iodine Radioisotopes; D019869:Phosphatidylinositol 3-Kinases; D012333:RNA, Messenger; D027981:Symporters; D000099209:Sodium-Iodide Symporters