Abstract
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 in the level of fibronectin receptor (α5β1 integrin) at the cell surface (Yan and Frenkel,Biol. Trace Element Res. 46, 79–89 [1994]). We have now found that after exposure to selenite, there was a decrease in the total cellular content of the receptor protein, as well as in the level of the mRNAs for both of the subunits. Exposure of cells to actinomycin D (an inhibitor of RNA synthesis) also resulted in a decrease in the level of these mRNAs, suggesting that the effect of selenite is the result of its known inhibitory effect on RNA synthesis (Frenkel,Toxicol. Lett. 25, 219–223 [1985]). Exposure of cells to actinomycin 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 fibronectin only when high-density cells were exposed to the agents. In contrast, when low-density cells were exposed,neither agent had any detectable effect on mRNA levels or on cell attachment. These results have suggested the following scheme for the mechanism of the inhibition of cell attachment by selenite: After exposure to selenite for 2 h, there is a significant inhibition of cellular RNA synthesis, which results in a general decrease in the cellular level of those mRNAs with relatively short half-lives, including in particular those of the fibronectin receptor. This leads to a decrease in the intracellular level of the receptor protein and, consequently, in its level at the cell surface, which in turn causes a decrease in the rate of cell attachment to fibronectin.
Similar content being viewed by others
References
M. A. Schwartz and D. E. Ingber, Integrating with integrins,Mol Biol. Cell 5, 389–393 (1994).
C. Rosales, V. O’Brian, L. Kornberg, and R. Juliano, Signal transduction by cell adhesion receptors,Biochim. Biophys. Acta 1242, 77–98 (1995).
L. Yan and G. D. Frenkel, Effect of selenite on cell surface fibronectin receptor,Biol. Trace Element Res. 46, 79–89 (1994).
R. Pytela, M. D. Pierschbacher, and E. Ruoslahti, Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor,Cell 40, 191–198 (1985).
L. Yan and G. D. Frenkel, Inhibition of cell attachment by selenite,Cancer Res. 52, 5803–5807 (1992).
Y. Gong and G. D. Frenkel, Effect of selenite on tumor cell invasiveness,Cancer Lett. 78, 196–199 (1994).
M. J. Humphries, K. Olden, and K. M. Yamada, A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells,Science 233, 467–470 (1986).
C. MacVicar and G. D. Frenkel, Effect of cell density on the inhibition of tumor cell attachment and nucleic acid synthesis by selenite,Biol. Trace Element Res. 39, 139–147 (1993).
R. R. Isberg and J. M. Leong, Multiple β1 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells,Cell 60, 861–871 (1990).
U. K. Laemmli, Cleavage of structural proteins during the assembly of the head of bacteriophage T4,Nature 227, 680–685 (1970).
P. Chomczynski and N. Sacchi, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction,Anal. Biochem. 162, 156–159 (1987).
D. Medina, D. Morrison, and C. J. Oborn, Selenium retention and inhibition of cell growth in mouse mammary epithelial cell linein vitro, Biol. Trace Element Res. 8, 19–35 (1985).
M. E. Fico, K. A. Poirier, A. Watrach, M. Watrach, and J. A. Milner, Differential effects of selenium on normal and non-neoplastic mammary cells,Cancer Res. 46, 3384–3388 (1986).
M. J. Kuchan and J. A. Milner, Influence of intracellular glutathione on selenitemediated growth inhibition of canine mammary tumor cells,Cancer Res. 52, 1091–1095 (1992).
L. Yan, J. A. Yee, M. H. McGuire, and G. L. Graef, Effect of dietary supplementation of selenite on pulmonary metastasis of melanoma cells in mice,Nutr. Cancer 28, 165–169 (1997).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zhu, M., Gong, Y. & Frenkel, G.D. Studies on the mechanism of the selenite-induced decrease in cell attachment. Biol Trace Elem Res 62, 123–134 (1998). https://doi.org/10.1007/BF02783966
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02783966