title: Epidermal growth-factor-induced transcript isoform variation drives mammary cell migration.
abstract: 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.
authors: Departments of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors: Wolfgang J
authors: WJ
authors: Köstler
authors: Amit
authors: A
authors: Zeisel
authors: Cindy
authors: C
authors: Körner
authors: Jonathan M
authors: JM
authors: Tsai
authors: Jasmine
authors: J
authors: Jacob-Hirsch
authors: Nir
authors: N
authors: Ben-Chetrit
authors: Kirti
authors: K
authors: Sharma
authors: Hadas
authors: H
authors: Cohen-Dvashi
authors: Assif
authors: A
authors: Yitzhaky
authors: Eric
authors: E
authors: Lader
authors: Ulrich
authors: U
authors: Tschulena
authors: Gideon
authors: G
authors: Rechavi
authors: Eytan
authors: E
authors: Domany
authors: Stefan
authors: S
authors: Wiemann
authors: Yosef
authors: Y
authors: Yarden
mesh_terms: D017398:Alternative Splicing; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005091:Exons; D005260:Female; D014644:Genetic Variation; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D026723:Polyadenylation; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor