title: Induction of BAIAP3 by the EWS-WT1 chimeric fusion implicates regulated exocytosis in tumorigenesis.
abstract: Desmoplastic small round cell tumor (DSRCT) is defined genetically by the chimeric fusion of the Ewing's sarcoma and Wilms' tumor genes, generating a novel transcription factor, EWS-WT1. By using cells with inducible EWS-WT1 to screen high-density microarrays, we identified BAIAP3 as a transcriptional target of the chimera. The BAIAP3 promoter is specifically bound in vivo by the (-KTS) isoform of EWS-WT1, consistent with its activation in reporter assays. BAIAP3 encodes a protein implicated in regulated exocytosis, which is colocalized with a secreted growth factor within cytoplasmic organelles. Ectopic expression of BAIAP3 in tumor cells dramatically enhances growth in low serum and colony formation in soft agar. BAIAP3 therefore encodes a transcriptional target of an oncogenic fusion protein that implicates the regulated exocytotic pathway in cancer cell proliferation.
authors.affiliation: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Palmer
authors.forename: Sean Bong
authors.initials: SB
authors.lastname: Lee
authors.forename: Jenise C
authors.initials: JC
authors.lastname: Wong
authors.forename: Paul A
authors.initials: PA
authors.lastname: Reynolds
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Vivi
authors.initials: V
authors.lastname: Truong
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Oliner
authors.forename: William L
authors.initials: WL
authors.lastname: Gerald
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
mesh_terms: D020533:Angiogenesis Inhibitors; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005089:Exocytosis / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D016162:Genes, Wilms Tumor; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009030:Mosaicism; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D034802:RNA-Binding Protein EWS / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000648:ultrastructure
chemical_list: D020533:Angiogenesis Inhibitors; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D034802:RNA-Binding Protein EWS