title: Identification of ETS-1 target genes in human fibroblasts.
abstract: The transcription factor Ets-1 plays several distinct critical roles in tumour development and progression by acting both in neoplastic cells and in the tumour stroma. Increased expression of Ets-1 in tumours is often associated with a worse prognosis. Stromal fibroblasts attribute an important part to the behaviour of malignant tumours. In this study we investigated the role of Ets-1 in the tumour stroma. It is well known that ets-1 expression in fibroblasts--one of the main components of the tumour stroma--can be induced by basic fibroblast growth factor (bFGF). We applied suppression subtractive hybridization (SSH) to identify genes that are differentially expressed between bFGF stimulated wild-type fibroblasts and fibroblasts with reduced Ets-1 expression. We selected clones up- or down-regulated in bFGF stimulated wild-type fibroblasts using SSH and functionally characterized them by reference to public databases using NCBI BLAST tools. Expression levels of genes corresponding to subtracted clones were analyzed using RT-PCR. Known genes were associated with diverse functions; novel Ets-1 regulated genes identified by SSH not only encoded components involved in matrix degradation (as cathepsin and PAI-2) but also constituents of the extracellular matrix (ECM) including α-2-Type I collagen, TGF-β induced protein, lumican and decorin. Our findings identify several potential novel target genes of Ets-1, and they provide potentially important insights into the role of Ets-1 in stromal fibroblasts for both remodelling and different functionalities of the ECM.
authors.affiliation: Universitätsfrauenklinik Würzburg, D-97080 Würzburg, Germany.
authors.forename: Jens Claus
authors.initials: JC
authors.lastname: Hahne
authors.forename: Ali Fuat
authors.initials: AF
authors.lastname: Okuducu
authors.forename: Tanja
authors.initials: T
authors.lastname: Fuchs
authors.forename: Alexandra
authors.initials: A
authors.lastname: Florin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wernert
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D016212:Transforming Growth Factor beta