Induction of BAIAP3 by the EWS-WT1 chimeric fusion implicates regulated exocytosis in tumorigenesis

R Palmer, S Lee, J Wong, Paul Andrew Reynolds, H Zhang, V Truong, J Oliner, W Gerald, D Haber

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)497-505
Number of pages9
JournalCancer Cell
Volume2
Issue number6
DOIs
Publication statusPublished - Dec 2002

Keywords

  • ROUND-CELL TUMOR
  • FIBROBLAST-GROWTH-FACTOR
  • BOVINE CHROMAFFIN CELLS
  • TRANSCRIPTIONAL ACTIVATOR
  • DNA-BINDING
  • WILMS-TUMOR
  • SUPPRESSOR GENE
  • PC12 CELLS
  • WT1 GENE
  • PROTEIN

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