Contributions of selenoproteins to breast cancer etiology and racial disparity

Abstract

Purpose Breast cancer etiology is multifactorial with African American women experiencing a significant health disparity in clinical presentation and outcomes. The selenium-containing protein SELENOF has been implicated in breast carcinogenesis by cell culture and animal studies. SELENOF translation is highly regulated in part by the RNA helicase eIF4a3, which binds to the key regulatory regions in the SELENOF mRNA and suppress its translation. In addition, SELENOP, the primary selenium transporter, plays a critical role in selenium delivery to tissues and may influence selenoprotein synthesis. This study aimed to examine the levels of SELENOF and eIF4a3, along with SELENOF and SELENOP genotypes, in breast cancer tissues from African American and Caucasian women Methods To study their roles in breast cancer outcome and racial disparity, human tissues were assessed by multiplex immunofluorescence staining with antibodies directed against SELENOF and eIF4a3 and DNA from these tissues were genotyped for previously studied variations in SELENOF and the selenium transporter protein SELENOP Results Elevated levels of both SELENOF and eIF4a3 were observed in breast cancer tissues. SELENOF expression and genotype varied by HER2 status, while SELENOP genotypes were associated with breast cancer and showed age-related differences. SELENOF and eIF4a3 were also higher in tissues derived from African American women, who also exhibited higher frequency of a SELENOP polymorphism in the non-coding region of the gene Conclusion These findings suggest that SELENOF, eIF4a3, and SELENOP may contribute to breast cancer progression and racial disparities in outcomes. Their differential expression and genetic variation highlight potential molecular mechanisms underlying these disparities and may inform future therapeutic or diagnostic strategies.

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