Analysis of Human Sodium Iodide Symporter Gene Expression in Extrathyroidal Tissues and Cloning of Its Complementary Deoxyribonucleic Acids from Salivary Gland, Mammary Gland, and Gastric Mucosa
C. Spitzweg,
W. Joba,
W. Eisenmenger and
A. E. Heufelder
Molecular Thyroid Research Unit Medizinische Klinik (C.S., W.J.,
A.E.F.), and Department of Legal Medicine (W.E.), Klinikum Innenstadt,
Ludwig-Maximilians-Universität, 80336 München, Germany
Address all correspondence and requests for reprints to: A. E. Heufelder, M.D., Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität, Ziemssenstr. 1, 80336 München, Germany. E-mail: u7g11av{at}mail.lrz-muenchen.de
The ability to concentrate iodide is a fundamental propertyof normally
functioning thyroid tissue and represents the firststep in the
production of thyroid hormones. Iodide uptake hasbeen demonstrated in
various extrathyroidal tissues, includingsalivary gland, gastric
mucosa, and lactating mammary gland.Recently, cloning and molecular
characterization of the humansodium iodide symporter (hNIS) have been
reported; however,the patterns of hNIS gene expression in human
tissues have remainedunidentified. To examine the profiles of human
hNIS gene expressionin various normal human tissues, we performed
high-stringencyNorthern blot analysis using a 32P-labeled
hNIS-specific complementaryDNA (cDNA) probe (nucleotides 1184–1667).
To detect rarehNIS transcripts in small tissue samples, RT-PCR was
performedwith a pair of hNIS-specific oligonucleotide primers designed
toamplify a portion (nucleotides 1184–1667) of the hNISgene.
hNIS-specific transcripts were confirmed by Southern hybridization
usinga digoxigenin-labeled internal hNIS-specific oligonucleotide
probe(nucleotides 1460–1477). To monitor cDNA integrity andquantity,
and to rule out DNA contamination and illegitimatetranscription, all
samples were coamplified with two pairs ofintron-spanning primers
designed to amplify fragments of thehuman ß-actin and thyroglobulin
genes, respectively. UsingNorthern blot analysis, hNIS transcripts of
approximately 4kb were detected in thyroid gland and parotid gland but
notin a broad range of endocrine and nonendocrine tissues. RT-PCRand
Southern hybridization revealed hNIS gene expression inthyroid gland,
salivary gland, parotid gland, submandibulargland, pituitary gland,
pancreas, testis, mammary gland, gastricmucosa, prostate and ovary,
adrenal gland, heart, thymus, andlung. By contrast, hNIS transcripts
were not detected in normalorbital fibroblasts, colon, and
nasopharyngeal mucosa. To furtheranalyze hNIS gene sequences in
parotid gland, mammary gland,and gastric mucosa, the EXPAND High
Fidelity PCR System andthree sets of overlapping NIS oligonucleotide
primers were usedfor amplification and cloning. The resulting PCR
products weresubcloned into pBluescript-SK II (-) vector, and at
least twoindependent cDNA clones derived from each tissue were
subjectedto automated sequencing. The nucleotide sequences of hNIS
cDNAderived from parotid gland, mammary gland, and gastric mucosa
revealedfull identity with the recently published human
thyroid-derivedNIS cDNA sequence. In conclusion, our results
demonstrate markedlyvariable levels of hNIS gene expression in several
extrathyroidaltissues. Although the physiological role of hNIS in
these tissuesawaits further study, our results suggest that the
capacityto actively transport iodine may be a feature common to
severalsecretory and endocrine tissues. The diminished capacity to
transportand concentrate iodide in extrathyroidal tissues (such as
parotidgland, mammary gland, and gastric mucosa), compared with
thyroidgland, does not seem to be caused by an altered primary
structureof the hNIS cDNA. Variability of NIS gene expression levels
innormal extrathyroidal tissues may rather be caused by differencesin
NIS gene transcriptional activity. Further studies will addressthis
hypothesis and examine the mechanisms of tissue-specificregulation of
NIS gene expression.
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