title: Evaluation of effects caused by differentially spliced Ets-1 transcripts in fibroblasts.
abstract: The transcription factor Ets-1 is known to be involved in a broad variety of cellular functions such as cell proliferation, migration, invasion, apoptosis and angiogenesis. In nearly all these reports, the full-length Ets-1 (p51) is commonly considered to be the active form and the role of the Ets-1ΔVII splice variant (p42) has not been addressed. Therefore, we studied the functional effects of p42 Ets-1 in comparison to p51 Ets-1 expression in a well-characterized mouse fibroblast cell line. Furthermore, the specific role of Ets-1 was evaluated using mouse fibroblasts with a reduced Ets-1 expression caused by RNAi and compared to fibroblasts with a binding inhibition of the whole ETS transcription factor family by stably overexpressing the ETS DNA binding domain as transdominant-negative mutant. Our results demonstrate that p42 Ets-1 has quite different functions and target genes compared to p51 Ets-1 (e.g. TIMP-4, MMP-3, MMP-9, MMP-13). In some cases (e.g. in cytokine expression) p42 Ets-1 is a functional transcription factor which acts in the same manner as a transdominant-negative approach.
authors.affiliation: Department of Obstetrics and Gynecology, University of Würzburg, D-97080 Würzburg, Germany.
authors.forename: Jens Claus
authors.initials: JC
authors.lastname: Hahne
authors.forename: Tanja
authors.initials: T
authors.lastname: Fuchs
authors.forename: Alexandra
authors.initials: A
authors.lastname: Florin
authors.forename: Dylan
authors.initials: D
authors.lastname: Edwards
authors.forename: Albin
authors.initials: A
authors.lastname: Pourtier
authors.forename: Fabrice
authors.initials: F
authors.lastname: Soncin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wernert
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D021381:Protein Transport; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D050784:Proto-Oncogene Protein c-ets-1