Abstract
Epidemiological evidence has indicated an inverse association between selenium status and various types of cancer, including breast cancer. Selenoproteins are the primary mediators of selenium effects in human health. We have previously reported loss of heterozygosity in breast tumor samples of the gene for one of the selenoproteins, SELENOF. The function of SELENOF remains unclear and whether SELENOF levels impact breast cancer risk or outcome is unknown. The mining of breast cancer patient databases revealed that SELENOF mRNA is significantly lower in late-stage tumor samples and lower levels of SELENOF also predict poor patient outcome from breast cancer. Genetically manipulating SELENOF in human breast cancer cells or in the murine mammary gland by overexpression, silencing or knockout impacted cell viability by affecting both proliferation and cell death. Restoring SELENOF can attenuate a number of aggressive cancer phenotypes in breast cancer cells, including clonogenic survival, and enhance the response to drugs or radiation used in breast cancer therapy. Importantly, enhancing SELENOF expression reduced in vivo tumor growth in a murine xenograft model of breast cancer. These data indicate that SELENOF is a new tumor suppressor in breast cancer.
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Acknowledgements
We thank Dr. Vadim Gladyshev for the Selenof−/− mice as well as Yves Helou (UIC) and Patricia Simms (LUC) for their technical assistance.
Funding
This work was supported by LUC funds to IK and by the Office of the Assistant Secretary of Defense for Health Affairs through the Prostate Cancer Research Program under Award No. W81XWH-17-PCRP-HDRA to AMD. These funding sources had no involvement in the data presented here.
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AZ: Methodology, Investigation, Analysis. LKH: Methodology, Investigation. RCE: Methodology, Investigation, Validation. CC-A: Investigation. EG: Investigation, Validation. AMD: Conceptualization, Supervision, Methodology, Formal Analysis, Review and Editing, Funding Acquisition. IK: Conceptualization, Supervision, Methodology, Investigation, Formal Analysis, Writing Original Draft, Funding Acquisition. All authors read and approved the final manuscript.
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Zigrossi, A., Hong, L.K., Ekyalongo, R.C. et al. SELENOF is a new tumor suppressor in breast cancer. Oncogene 41, 1263–1268 (2022). https://doi.org/10.1038/s41388-021-02158-w
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DOI: https://doi.org/10.1038/s41388-021-02158-w
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