An expression vector containing a cDNA complementary to 1.3 kb of the 5' coding sequences of the fibronectin gene in the antisense orientation with respect to its promoter was introduced by electroporation into hybrids between melanoma cells and normal fibroblasts in which malignancy was suppressed. Immunofluorescence analysis of clones transfected with the antisense cDNA showed a dramatic decrease in the amount of fibronectin on the cell surface compared to that seen on the surface of the untransfected hybrid cells or of cells transfected with fibronectin cDNA in the sense orientation or with the expression vector alone. Four out of five clones transfected with the antisense cDNA were highly tumorigenic, whereas transfectants containing either the sense fibronectin construct or the expression vector alone remained non-tumorigenic. These results suggest that antisense RNA to fibronectin may be able to abrogate the suppression of malignancy imposed on the hybrid cells by the fibroblast parent.
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