Transforming growth factor-alpha antisense vectors can inhibit glioma cellgrowth

The effects of transforming growth factor-alpha (TGF-alpha) on cell growth were studied in human glioma U251 cells transfected with antisense TGF-alph a vectors (pcDNAI.neo). Several antisense clones showed a marked decrease i n growth rate in serum-free medium but not in medium containing 10% FBS, co mpared with those of parental cells and clones from sense or vector transfe ctants. Antisense clones also produced fewer and smaller colonies in anchor age-independent growth assays. Moreover, there was a reduction in TGF-alpha expression in these antisense clones at both the protein and mRNA levels, as determined by enzyme linked immuno-sorbent assay and reverse transcripta se polymerase chain reaction analysis. A U251 clone transfected by TGF-alph a antisense in a different vector (pMT/Ep) also showed a marked suppression in cell growth and TGF-alpha mRNA level. Finally, transfected clones with either vector system, showed decreased tumorigenicity in nude mice. In summ ary, a strong correlation between the inhibition of glioma cell growth and TGF-alpha expression was obtained from two different plasmid vectors, indic ating that the expression of TGF-alpha could be specifically and effectivel y down-regulated by TGF-alpha antisense vector, which in turn led to growth inhibition. These studies suggests that TGF-alpha plays an essential role in controlling human glioma cell proliferation and may serve as a potential target for treatment of malignant glioma.