CELL-CYCLE DEPENDENT ALTERNATIVE SPLICING OF THE TENASCIN PRIMARY TRANSCRIPT

Functionally different tenascin (TN) isoforms may be generated by alte rnative splicing of the TN primary transcript. In fact, it has been de monstrated that only the larger TN isoform containing the alternativel y spliced region induces loss of focal adhesion in cultured cells and seems able to facilitate cell migration. Recent studies have shown tha t the higher molecular mass TN isoform is a marker of stromal cell pro liferation in hyperplastic and neoplastic breast tissues. This finding prompted us to study the pattern of TN alternative splicing in prolif erating and non-proliferating cultured fibroblasts. Here, we show that the mitogenic stimulation of fibroblasts with serum or cytokines lead s to an early and striking modification in the steady-state levels of the two major TN mRNAs. We also show that de novo protein synthesis is not necessary for this modification, indicating that it is a ''primar y response'' event. Similarly, mitogenic stimulation induces changes b oth in synthesis and accumulation of the different TN isoforms.