Tumor suppressor protein p53 exerts negative transcriptional regulation on human sodium iodide symporter gene expression in breast cancer

Breast Cancer Research and Treatment
Madhura G KelkarAbhijit De

Abstract

Aberrant expression of human sodium iodide symporter (NIS) in breast cancer (BC) is well documented but the transcription factors (TF) regulating its aberrant expression is poorly known. We identify the presence of three p53 binding sites on the human NIS promoter sequence by conducting genome-wide TF analysis, and further investigate their regulatory role. The differences in transcription and translation were measured by real-time PCR, luciferase reporter assay, site-directed mutagenesis, in vivo optical imaging, and chromatin immunoprecipitation. The relation of NIS and p53 in clinical samples was judged by TCGA data analysis and immunohistochemistry. Overexpression of wild-type p53 as a transgene or pharmacological activation by doxorubicin drug treatment shows significant suppression of NIS transcription in multiple BC cell types which also results in lowered NIS protein content and cellular iodide intake. NIS repression by activated p53 is further confirmed by non-invasive bioluminescence imaging in live cell and orthotropic tumor model. Abrogation of p53-binding sites by directional mutagenesis confirms reversal of transcriptional activity in wild-type p53-positive BC cells. We also observe direct binding of p53 to these ...Continue Reading

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Citations

Dec 14, 2018·Cancer Biotherapy & Radiopharmaceuticals·Zhi-Yuan ZhuDa-Peng Li
Aug 23, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jun ZouZhi-Gang Jie
Jul 7, 2018·World Journal of Surgical Oncology·Liangbo DongYupei Zhao
May 20, 2021·Journal of Cellular and Molecular Medicine·Jun ZhangQinliang Zhang

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