SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells.

SELENOF expression is significantly lower in aggressive breast tumors compared to normal tissue, indicating that its reduction or loss may drive breast tumorigenesis. Deletion of SELENOF in non-tumorigenic immortalized breast epithelial MCF-10A cells resulted in enhanced proliferation, both in adherent culture and matrix-assisted three-dimmensional (3D) growth. Modulation of SELENOF in vitro through deletion or overexpression corresponded to changes in the cell-cycle regulators p21 and p27, which is consistent with breast tumor expression data from the METABRIC patient database. Together, these findings indicate that SELENOF affects both proliferation and cell death in normal epithelial and breast cancer cells, largely through the regulation of p21 and p27. In glandular cancers like breast cancer, the filling of luminal space is one of the hallmarks of early tumorigenesis. Loss of SELENOF abrogated apoptosis and autophagy, which are required for the formation of hollow acini in MCF-10A cells in matrix-assisted 3D growth, resulting in luminal filling. Conversely, overexpression of SELENOF induced cell death via apoptosis and autophagy. In conclusion, these findings are consistent with the notion that SELENOF is a breast tumor suppressor, and its loss contributes to breast cancer etiology.

Distinct Roles of SELENOF in Different Human Cancers.

SELENOF, previously known as SEP15, is a selenoprotein that contains selenium in the form of the amino acid selenocysteine. Like other selenoproteins, the role for SELENOF in carcinogenesis has been investigated due to its altered expression compared to the corresponding normal tissue, its molecular function, and the association of genetic variations in the SELENOF gene to cancer risk or outcome. This review summarizes SELENOF's discovery, structure, cellular localization, and expression. SELENOF belongs to a new family of thioredoxin-like proteins. Published data summarized here indicate a likely role for SELENOF in redox protein quality control, and in the regulation of lipids, glucose, and energy metabolism. Current evidence indicates that loss of SELENOF contributes to the development of prostate and breast cancer, while its loss may be protective against colon cancer. Additional investigation into SELENOF's molecular mechanisms and its impact on cancer is warranted.

Selenium and breast cancer - An update of clinical and epidemiological data.

There is an urgent need for new and improved therapeutic strategies in breast cancer, which is the most common malignancy affecting women in the United States and worldwide. Selenium (Se) is an essential trace element of the human diet and plays a critical role in many aspects of human health. Clinical and epidemiological studies summarized here clearly demonstrate that Se status correlates with breast cancer survival. As a result, one way to curb breast cancer mortality would be via Se supplementation, especially in patients with severely deplete Se status. Se manifests its biological activity through incorporation into selenoproteins as selenocysteine. However, a better understanding of tissue-specific mechanisms and roles for selenoproteins in general is required. Additionally, many human selenoproteins harbor single nucleotide polymorphisms, which impact protein expression and activity and have been associated with cancer susceptibility or impacting survival. Increasing evidence indicates that these genetic variations impinge on the interactions between Se and breast cancer. This highlights the importance of integrating the Se status with genetic factors to fully define the benefit of Se in breast cancer. While Se supplementation would clearly benefit a subset of patients, this requires first the identification of at-risk patients and warrants validation through intervention trials.