STUDIES ON THE MECHANISM OF THE SELENITE-INDUCED DECREASE IN CELL ATTACHMENT - EFFECT OF SELENITE ON THE LEVELS OF FIBRONECTIN RECEPTOR (ALPHA-5-BETA-1 INTEGRIN) MESSENGER-RNAS

We previously reported that exposure of HeLa cells to selenite for 2 h results in a decrease in their ability to attach to fibronectin (Yan and Frenkel, Cancer Res. 52, 5803-5807 (1992), as well as a decrease i n the level of fibronectin receptor (alpha 5 beta 1 integrin) at the c ell surface (Yan and Frenkel, Biol. Trace Element Res. 46, 79-89 [1994 ]). We have now found that after exposure to selenite, there was a dec rease in the total cellular content of the receptor protein, as well a s in the level of the mRNAs for both of the subunits. Exposure of cell s to actinomycin D tan inhibitor of RNA synthesis) also resulted in a decrease in the level of these mRNAs, suggesting that the effect of se lenite is the result of its known inhibitory effect on RNA synthesis ( Frenkel, Toxicol. Lett. 25, 219-223 [1985]). Exposure of cells to acti nomycin D for 2 h also resulted in a decrease in the ability of cells to attach to fibronectin. Furthermore, both selenite and actinomycin D caused a decrease in integrin mRNA levels and in cell attachment to f ibronectin only when high-density cells were exposed to the agents. in contrast, when low-density cells were exposed,neither agent had any d etectable effect on mRNA levels or on cell attachment. These results h ave suggested the following scheme for the mechanism of the inhibition of cell attachment by selenite: After exposure to selenite for 2 h, t here is a significant inhibition of cellular RNA synthesis, which resu lts in a general decrease in the cellular level of those mRNAs with re latively short half-lives, including in particular those of the fibron ectin receptor. This leads to a decrease in the intracellular level of the receptor protein and, consequently, in its level at the cell surf ace, which in turn causes a decrease in the rate of cell attachment to fibronectin.