| 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. Copyright © 2002 Cell Press. |
| Keywords: |
osteosarcoma; controlled study; protein expression; unclassified drug; oncoprotein; human cell; promoter region; genetics; angiogenesis inhibitor; cancer growth; molecular genetics; protein localization; cell proliferation; proteins; animal; metabolism; animals; gene; gene targeting; culture medium; protein; transcription factor; genetic transcription; transcription, genetic; tumor cells, cultured; physiology; carcinogenesis; cell transformation, neoplastic; ewing sarcoma; chimera; gene expression regulation; in situ hybridization; oncogene; tumor suppressor gene; gene expression regulation, neoplastic; molecular sequence data; cell culture; cell transformation; nucleotide sequence; cancer cell; gene fusion; oncogene proteins, fusion; protein induction; base sequence; dna microarray; density; angiogenesis inhibitors; rna binding protein ews; blotting, northern; genetic code; serum; ultrastructure; cell organelle; nephroblastoma; small cell carcinoma; exocytosis; northern blotting; carcinoma, small cell; rna-binding protein ews; colony forming cell; mosaicism; promoter regions (genetics); genes, wilms tumor; humans; human; priority journal; article; brain angiogenesis inhibitor activator protein 3; ewing sarcoma wilm tumor gene
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