Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation?
BACKGROUND
Sodium/iodide symporter (NIS) is a key protein in iodide transport by thyroid cells and this activity is a prerequisite for effective radioiodide treatment of thyroid cancer. In the majority of thyroid cancers, however, iodide uptake is reduced, probably as a result of decreased NIS protein expression.


METHODS
To identify the mechanisms that negatively affect NIS expression in thyroid tumors, we performed electrophoresis mobility shift assays and immunoblot analysis of nuclear protein extracts from normal and tumoral thyroid tissues from 14 unrelated patients.


RESULTS
Two proteins closely related to the transcription factors AP2 and Sp1 were identified in the nuclear extracts. Expression of both AP2 and Sp1 in nuclear extracts from thyroid tumors was significantly higher than that observed in corresponding normal tissues.


CONCLUSIONS
These observations raise the possibility that NIS expression, and subsequently iodide transport, are reduced in thyroid tumors at least in part owing to alterations in the binding activity of AP2 and Sp1 transcription factors to NIS promoter.
Chiefari
Eusebio
E
Department of Clinical Sciences, University of Roma La Sapienza, Roma, Italy. e.chiefari@tin.it
Brunetti
Antonio
A
Arturi
Franco
F
Bidart
Jean-Michel
JM
Russo
Diego
D
Schlumberger
Martin
M
Filetti
Sebastiano
S
D000236:Adenoma / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018265:Carcinoma, Papillary, Follicular / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002457:Cell Extracts / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000099209:Sodium-Iodide Symporters
D002457:Cell Extracts; D004268:DNA-Binding Proteins; D016329:Sp1 Transcription Factor; D027981:Symporters; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D000099209:Sodium-Iodide Symporters