EXTRACELLULAR PH CONTROLS PRE-MESSENGER-RNA ALTERNATIVE SPLICING OF TENASCIN-C IN NORMAL, BUT NOT IN MALIGNANTLY TRANSFORMED, CELLS

In cultured normal human fibroblasts, 2 main tenascin-C (TN-C) isoform s are generated by alternative splicing of the single TN-C primary tra nscript, 8 type III repeats being included or omitted in the mRNA. In these cultured cells, small pH variations of the culture medium (from 7.2 to 6.8) strikingly modify the alternative splicing pattern of the TN-C primary transcript. We report that malignantly transformed cells do not respond to extracellular pH variations as normal cells do. Inde ed, malignantly transformed cells kept in culture media at pH values f rom 6.6 to 7.6 show no variations in the splicing pattern of the TN-C primary transcript and accumulate almost exclusively the large TN-C mR NA. These observations may explain the preferential accumulation in vi va of the large TN-C isoform in the extracellular matrix of different types of neoplasia. (C) 1996 Wiley-Liss, Inc.