Abstract
Supplemental dietary selenium is associated with reduced incidence of many cancers. The antitumor function of selenium is thought to be mediated through selenium-binding protein 1 (SELENBP1). However, the significance of SELENBP1 expression in breast cancer is still largely unknown. A total of 95 normal and tumor tissues assay and 12 breast cancer cell lines were used in this study. We found that SELENBP1 expression in breast cancer tissues is reduced compared to normal control. Low SELENBP1 expression in ER+ breast cancer patients was significantly associated with poor survival (p<0.01), and SELENBP1 levels progressively decreased with advancing clinical stages of breast cancer. 17-β estradiol (E2) treatment of high SELENBP1-expressing ER+ cell lines led to a down-regulation of SELENBP1, a result that did not occur in ER– cell lines. However, after ectopic expression of ER in an originally ER– cell line, down-regulation of SELENBP1 upon E2 treatment was observed. In addition, selenium treatment resulted in reduced cell proliferation in endogenous SELENBP1 high cells; however, after knocking-down SELENBP1, we observed no significant reduction in cell proliferation. Similarly, selenium has no effect on inhibition of cell proliferation in low endogenous SELENBP1 cells, but the inhibitory effect is regained following ectopic SELENBP1 expression. Furthermore, E2 treatment of an ER silenced high endogenous SELENBP1 expressing cell line showed no abolishment of cell proliferation inhibition upon selenium treatment. These data indicate that SELENBP1 expression is regulated via estrogen and that the cell proliferation inhibition effect of selenium treatment is dependent on the high level of SELENBP1 expression. Therefore, the expression level of SELENBP1 could be an important marker for predicting survival and effectiveness of selenium supplementation in breast cancer. This is the first study to reveal the importance of monitoring SELENBP1 expression as a potential biomarker in contributing to breast cancer prevention and treatment.
Highlights
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women in the United States [1]
This result indicates that SELENBP1 expression is reduced in breast cancer tissue and it is not correlated with age
We found that breast cancer tumor tissues had reduced levels of SELENBP1 expression compared to normal tissue, with a significant decrease of SELENBP1 was confirmed in late-stage (Stage III) tumors
Summary
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women in the United States [1]. 75–80% of breast cancers express the estrogen receptor (ER), which can be targeted by selective estrogen receptor modulators such as tamoxifen or aromatase inhibitors to block estrogen action. Approximately 40% of patients fail to respond to current treatment strategies for breast cancer and die from the disease. Identification of more reliable markers to predict the effectiveness of specific therapies and understanding of the respective molecular mechanisms that enhance treatment efficacy are urgently needed. A number of potential mechanisms have been proposed for the preventative effects of Se, including stimulation of apoptosis, induction of cellcycle arrest, inhibition of tumor cell invasion, and influences on estrogen and androgen-receptor expression [5,6,7]
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