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Extracellular pH controls pre‐mRNA alternative splicing of tenascin‐C in normal, but not in malignantly transformed, cells
Author(s) -
Borsi Laura,
Allemanni Giorgio,
Gaggero Barbara,
Zardi Luciano
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960529)66:5<632::aid-ijc9>3.0.co;2-u
Subject(s) - extracellular , tenascin c , alternative splicing , extracellular matrix , messenger rna , biology , rna splicing , microbiology and biotechnology , chemistry , genetics , rna , gene
In cultured normal human fibroblasts, 2 main tenascin‐C (TN‐C) isoforms are generated by alternative splicing of the single TN‐C primary transcript, 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. Indeed, malignantly transformed cells kept in culture media at pH values from 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 mRNA. These observations may explain the preferential accumulation in vivo of the large TN‐C isoform in the extracellular matrix of different types of neoplasia. © 1996 Wiley‐Liss, Inc.