Selenoproteins that function in cancer prevention and promotion

Abstract

Of the many health benefits attributed to selenium, the one that has received the most attention is its role in cancer prevention. Selenium-containing proteins (selenoproteins) have been shown in recent years to have roles in cancer prevention. However, selenoproteins have diverse functions and their view as antioxidants is oversimplified. Some selenoproteins appear to have a split personality in having roles both in preventing and promoting cancer. The contrasting roles of one selenoprotein, thioredoxin reductase 1, in cancer are discussed in detail, but as also noted, at least one other selenoprotein may also have such a dual function. In addition, we discuss examples of inhibition of cancer development by selenoprotein deficiency in mouse models. These studies highlight the complex nature of selenium in relation to cancer.

Fig. 1

Tumorigenicity and metastasis of TR1 knockdown LLC1 cells. Mice were injected in either (A) the flank or (B) a tail vein with LLC1 cells expressing a control vector (designated control in the figure) or the same vector, but encoding the TR1 knockdown sequence (see reference [38] for details). In A1, tumor formation was monitored over a two week period and mice were euthanized and tumors weighed. In A2, Western blot analysis of TR1 levels in the two tumors in A1 (upper panel) and PCR analysis of genomic DNA from the tumors in A1 (lower panel). Clearly, TR1 is present in the smaller tumor generated in the TR1 knockdown LLC1 cells (upper panel). PCR analysis was carried out to identify the presence or absence of the control or knockdown vector in the tumor and the data show that the TR1 knockdown vector is lost from the tumor formed in mice injected with the knockdown vector (lower panel). Overall, these data demonstrate that TR1 expression is required for tumor formation in this experimental model. In A3, Western blot analysis of TR1 in LLC1 cells that were transfected with either the control vector or the TR1 knockdown vector prior to the injections of these cells into mice. The data illustrate the expression of TR1 in injected cells encoding the control or knockdown vector. In B1, metastasis was assessed after four weeks in the lungs of mice injected in their tails with LLC1 cells encoding either the control vector or the TR1 knockdown vector. The data show that TR1 expression is required for tumor formation in lungs following metastasis. In B2, tissue slices from the lungs in B1 are shown wherein pathological changes were observed in the tissue from of the control mice (see arrows), but not in the mice carrying the TR1 knockdown vector. The figure was taken with slight modification from reference with permission from the Journal of Biological Chemistry.