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Regulation of sodium/iodide symporter and lactoperoxidase expression in four human breast cancer cell lines
M Sponziello1, A Scipioni, C Durante
1Department of Clinical Sciences, University of Rome Sapienza, Rome, Italy.
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.
Aim:
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.
Insights
Retinoic acid and HDAC inhibitors show promise for radioiodine therapy in breast cancer. These agents stimulate sodium/iodide symporter (NIS) expression, enhancing radioiodine uptake in various breast cancer subtypes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Investigating agents to enhance radioiodine concentration via sodium/iodide symporter (NIS) stimulation for breast cancer treatment.
- Focus on well-differentiated breast cancers and agents targeting NIS expression.
Purpose of the Study:
- Analyze the regulation of NIS and lactoperoxidase (LPO) gene expression.
- Evaluate gene expression in four distinct human breast cancer cell lines representing different histotypes.
Main Methods:
- Utilized MCF-7, T-47D, MDA-MB231, and HCC-1937 (BRCA-1 mutation) breast cancer cell lines.
- Exposed cells to All-trans-Retinoic Acid (RA), Dexamethasone (DEX), Trichostatin A (TSA), and Sodium Butyrate (NaB).
- Quantified NIS and LPO mRNA levels using quantitative RT-PCR.
Main Results:
- RA, DEX, TSA, and NaB induced NIS mRNA in MCF-7 and T-47D cells.
- HCC-1937 and MDA-MB231 cells showed minimal response to TSA and NaB.
- Minor stimulatory effects on LPO mRNA were observed in MCF-7 and T-47D cells with TSA, NaB, or RA.
Conclusions:
- Retinoic acid (alone or with DEX) and HDAC inhibitors are promising for radioiodine therapy in diverse breast cancers.
- These agents are particularly effective for well-differentiated, estrogen-dependent tumors.
- Further research is needed to target less differentiated and aggressive tumor cells, including BRCA-mutated types.
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