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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.
AuthorsRachel E Palmer, Sean Bong Lee, Jenise C Wong, Paul A Reynolds, Hong Zhang, Vivi Truong, Jonathan D Oliner, William L Gerald, Daniel A Haber
JournalCancer cell (Cancer Cell) Vol. 2 Issue 6 Pg. 497-505 (Dec 2002) ISSN: 1535-6108 [Print] United States
PMID12498718 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Angiogenesis Inhibitors
  • Oncogene Proteins, Fusion
  • Proteins
  • RNA-Binding Protein EWS
Topics
  • Angiogenesis Inhibitors
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Carcinoma, Small Cell (genetics, metabolism)
  • Cell Transformation, Neoplastic (genetics)
  • Exocytosis (physiology)
  • Gene Expression Regulation, Neoplastic
  • Genes, Wilms Tumor
  • Humans
  • In Situ Hybridization
  • Molecular Sequence Data
  • Mosaicism
  • Oncogene Proteins, Fusion (genetics)
  • Osteosarcoma (genetics, metabolism)
  • Promoter Regions, Genetic
  • Proteins (genetics, metabolism)
  • RNA-Binding Protein EWS (genetics)
  • Transcription, Genetic
  • Tumor Cells, Cultured (ultrastructure)

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