Regulation of sodium/iodide symporter and lactoperoxidase expression in four human breast cancer cell lines.
BACKGROUND
Agents capable of increasing radioiodine concentration by stimulating the sodium/iodide symporter (NIS) expression have been extensively investigated for the treatment of certain well-differentiated breast cancers.


OBJECTIVE
In this study, we analyzed the regulation of the NIS and lactoperoxidase (LPO) gene expression in 4 different human breast cancer cell lines, representative of different histotypes of breast cancer.


METHODS
MCF-7, T-47D, MDA-MB231, and HCC-1937 (the latter carrying the BRCA-1 mutation) were exposed to different stimulators and the levels of NIS and LPO mRNA measured by a quantitative RT-PCR.


RESULTS
All-trans-Retinoic Acid (RA), Dexamethasone (DEX), Trichostatin A (TSA), and Sodium Butyrate (NaB) induced the expression of NIS mRNA in MCF-7 and T-47D cell lines, whereas HCC-1937 and MBA-MB231 were slightly responsive only to the histone-deacetylase inhibitors TSA and NaB. Minor stimulatory effects were detected on LPO mRNA in MCF-7 and T-47D treated with TSA and NaB or RA only in MCF-7, while no effect was detectable in the other two cell lines.


CONCLUSIONS
These data indicate that retinoic acid, alone or in combination with DEX, as well as HDAC-inhibitors are very promising agents for a radioiodine- based therapy in a large spectrum of breast cancers, including neoplasms from both basal and ductal cells, especially for the well-differentiated estrogen-dependent tumors. Other molecules or other drug combinations should be tested to extend the same strategy to the less differentiated and more aggressive tumor cells, including those carrying the BRCA mutation.
Sponziello
M
M
Department of Clinical Sciences, University of Rome Sapienza, Rome, Italy.
Scipioni
A
A
Durante
C
C
Verrienti
A
A
Maranghi
M
M
Giacomelli
L
L
Ferretti
E
E
Celano
M
M
Filetti
S
S
Russo
D
D
D001943:Breast Neoplasms / Q000378:metabolism*; D002087:Butyrates / Q000494:pharmacology; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007784:Lactoperoxidase / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology; D000099209:Sodium-Iodide Symporters
D002087:Butyrates; D003907:Dexamethasone; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007784:Lactoperoxidase; D012333:RNA, Messenger; D027981:Symporters; D014212:Tretinoin; D000099209:Sodium-Iodide Symporters; C012589:trichostatin A