ANTISENSE INHIBITION OF GLIAL S100-BETA PRODUCTION RESULTS IN ALTERATIONS IN CELL MORPHOLOGY, CYTOSKELETAL ORGANIZATION, AND CELL-PROLIFERATION

The phenotypic effects of selectively decreasing the levels of S100β in cultured glial cells were analyzed. Two separate antisense approaches were utilized for inhibition of S100β production; analysis of clonal isolates of rat C6 glioma cells containing an S100β antisense gene under the control of a dexamethasone-inducible promoter, and analysis of C6 cells treated with S100β antisense oligodeoxynucleotides. Both antisense methods resulted in a decrease in S100β levels in the cell, as measured by RIA. The inhibition of S100β production correlated with three alterations in cellular phenotype: (a) a flattened cell morphology; (b) a more organized microfilament network; and (c) a decrease in cell growth rate. The studies described here provide direct evidence for an involvement of S100β in glial cell structure and function, and suggest potential in vivo roles for S100β in regulation of glial cell morphology, cytoskeletal organization, and cell proliferation.