Selenoprotein expression is regulated at multiple levels in prostate cells

Abstract

Selenium supplementation in a population with low basal blood selenium levels has been reported to decrease the incidence of several cancers including prostate cancer. Based on the clinical findings, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect, although low molecular weight seleno-compounds have also been posited to selectively induce apoptosis in transformed cells. To address the effects of selenium supplementation on selenoprotein expression in prostate cells, we have undertaken an analysis of antioxidant selenoprotein expression as well as selenium toxicity in non-tumorigenic prostate epithelial cells (RWPE-1) and prostate cancer cells (LNCaP and PC-3). Our results show that two of the glutathione peroxidase family members (GPX1 and GPX4) are highly induced by supplemental selenium in prostate cancer cells but only slightly induced in RWPE-1 cells. In addition, GPX1 levels are dramatically lower in PC-3 cells as compared to RWPE-1 or LNCaP cells. GPX2 protein and mRNA, however, are only detectable in RWPE-1 cells. Of the three selenium compounds tested (sodium selenite, sodium selenate and selenomethionine), only sodium selenite shows toxicity in a physiological range of selenium concentrations. Notably and in contrast to previous studies, RWPE-1 cells were significantly more sensitive to selenite than either of the prostate cancer cell lines. These results demonstrate that selenoproteins and selenium metabolism are regulated at multiple levels in prostate cells.Cell Research (2006) 16:940-948.

The Selenocysteine-specific Elongation Factor Contains a Novel and Multi-functional Domain

“…Previously we have shown that PC-3 prostate cancer cells had reduced levels of the selenoprotein GPX1 compared with LNCaP prostate cancer cells and RWPE-1 nontumorigenic prostate cells (even when selenium levels were sufficient) suggesting that eEFSec and SBP2 may be limiting (17). We therefore first tested PC-3 lysates for Sec incorporation activity in the Sf21 system.…”

Structural Asymmetry of the Terminal Catalytic Complex in Selenocysteine Synthesis

“…Sec , HepG2 cells were grown to 80% confluence in DMEM supplemented with 50 nM sodium selenite, which is the dose typically used to support maximal selenoprotein production without toxic effects (46).…”

The differential expression of glutathione peroxidase 1 and 4 depends on the nature of the SECIS element

“…Our results obtained in Hek293 cells recapitulated what has been reported in other studies, either in rodents 20,32 or in human. 33 Interestingly, when comparing Dpl with Unsup extracts, the selenium deficiency led to a dramatic decrease of both Gpx1 and Gpx4 expression, although in the Dpl extract Gpx4 was still detectable while Gpx1 had almost disappeared. This effect uniquely depended on selenium concentration since cell growth in Dpl + Se media restored the expression of both Gpx1 and Gpx4 to the levels observed in Sup media.…”