Epidermal growth-factor-induced transcript isoform variation drives mammary cell migration.

Autor: Wolfgang J Köstler, Amit Zeisel, Cindy Körner, Jonathan M Tsai, Jasmine Jacob-Hirsch, Nir Ben-Chetrit, Kirti Sharma, Hadas Cohen-Dvashi, Assif Yitzhaky, Eric Lader, Ulrich Tschulena, Gideon Rechavi, Eytan Domany, Stefan Wiemann, Yosef Yarden
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: PLoS ONE, Vol 8, Iss 12, p e80566 (2013)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0080566
Popis: Signal-induced transcript isoform variation (TIV) includes alternative promoter usage as well as alternative splicing and alternative polyadenylation of mRNA. To assess the phenotypic relevance of signal-induced TIV, we employed exon arrays and breast epithelial cells, which migrate in response to the epidermal growth factor (EGF). We show that EGF rapidly--within one hour--induces widespread TIV in a significant fraction of the transcriptome. Importantly, TIV characterizes many genes that display no differential expression upon stimulus. In addition, similar EGF-dependent changes are shared by a panel of mammary cell lines. A functional screen, which utilized isoform-specific siRNA oligonucleotides, indicated that several isoforms play essential, non-redundant roles in EGF-induced mammary cell migration. Taken together, our findings highlight the importance of TIV in the rapid evolvement of a phenotypic response to extracellular signals.
Databáze: Directory of Open Access Journals