Induction of BAIAP3 by the EWS-WT1 Chimeric Fusion Implicates Regulated Exocytosis in Tumorigenesis

Cancer Cell. 2002 Dec;2(6):497-505. doi: 10.1016/s1535-6108(02)00205-2.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Carcinoma, Small Cell / genetics*
  • Carcinoma, Small Cell / 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
  • Osteosarcoma / metabolism
  • Promoter Regions, Genetic
  • Proteins / genetics*
  • Proteins / metabolism*
  • RNA-Binding Protein EWS / genetics
  • Transcription, Genetic
  • Tumor Cells, Cultured / ultrastructure

Substances

  • Angiogenesis Inhibitors
  • Oncogene Proteins, Fusion
  • Proteins
  • RNA-Binding Protein EWS

Associated data

  • GENBANK/AB017111
  • GENBANK/BB609845