Enhancement of human sodium iodide symporter gene therapy for breast cancer by HDAC inhibitor mediated transcriptional modulation

Scientific Reports
Madhura G KelkarAbhijit De

Abstract

The aberrant expression of human sodium iodide symporter (NIS) in breast cancer (BC) has raised the possibility of using targeted radioiodide therapy. Here we investigate modulation of endogenous, functional NIS expression by histone deacetylase inhibitors (HDACi) in vitro and in vivo. Luciferase reporter based initial screening of six different HDACi shows 2-10 fold enhancement of NIS promoter activity in majority of the cell types tested. As a result of drug treatment, endogenous NIS transcript and protein shows profound induction in BC cells. To get an insight on the mechanism of such transcriptional activation, role of Stat4, CREB and other transcription factors are revealed by transcription factor profiling array. Further, NIS-mediated intracellular iodide uptake also enhances substantially (p < 0.05) signifying functional relevance of the transcriptional modulation strategy. Gamma camera imaging confirms 30% higher uptake in VPA or NaB treated BC tumor xenograft. Corroborating with such functional impact of NIS, significant reduction in cell survival (p < 0.005) is observed in VPA, NaB or CI994 drug and (131)I combination treatment in vivo indicating effective radioablation. Thus, for the first time this study reveals the...Continue Reading

References

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Citations

Mar 22, 2018·Journal of Clinical Medicine·Sabine WächterPietro Di Fazio
Jul 2, 2016·Current Opinion in Endocrinology, Diabetes, and Obesity·Peter P A Smyth
Mar 25, 2020·Nuclear Medicine and Molecular Imaging·Aisyah ElliyantiWirsma Arif Harahap
Jul 7, 2018·World Journal of Surgical Oncology·Liangbo DongYupei Zhao
Sep 3, 2017·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·James NagarajahWalter Jentzen
Mar 7, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Ajit C DhadvePritha Ray

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Methods Mentioned

BETA
acetylation
transfection
PCR
xenograft
histone acetylation

Software Mentioned

ImageJ
GraphPad Prism
Genomatix
Transfac

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