Fold of induction was normalized against that of the vector reporter without an activator
| (A) Selected genes with PAX3-FKHR binding sites | ||||||||
|---|---|---|---|---|---|---|---|---|
| ID | Entrez gene name | Location | Type | Drugs | ||||
| Self-renewal, growth, survival, oncogenesis | ||||||||
| ALK | Anaplastic lymphoma receptor tyrosine kinase | Plasma membrane | Receptor kinase | PF-02341066 | ||||
| FGFR2 | Fibroblast growth factor receptor 2 | Plasma membrane | Receptor kinase | TKI-258, AZD2171, brivanib, PHA-739358 | ||||
| FGFR4 | Fibroblast growth factor receptor 4 | Plasma membrane | Receptor kinase | |||||
| IGF1R | Insulin-like growth factor 1 receptor | Plasma membrane | Receptor kinase | CP-751871, AMG479, R1507, MK-0646, AVE1642 | ||||
| KDR | Kinase insert domain receptor, VEGFR2 | Plasma membrane | Receptor kinase | Bevacizumab, sunitinib, vatalanib, sorafenib, vandetanib | ||||
| MEIS1 | Meis homeobox 1 | Nucleus | Transcription factor | |||||
| MYCN | v-myc myelocytomatosis viral related oncogene, neuroblastoma-derived | Nucleus | Transcription factor | |||||
| SPRY1 | Sprouty homologue 1, antagonist of FGF signaling (Drosophila) | Plasma membrane | FGFR4 ligand | |||||
| Migration, metastasis | ||||||||
| CXCR4 | Chemokine (C-X-C motif) receptor 4 | Plasma membrane | GPCR | JM 3100 | ||||
| MET | met proto-oncogene (hepatocyte growth factor receptor) | Plasma membrane | Receptor kinase | PF-02341066 | ||||
| Myogenic differentiation | ||||||||
| EYA2 | Eyes absent homologue 2 (Drosophila) | Nucleus | Phosphatase | |||||
| EYA4 | Eyes absent homologue 4 (Drosophila) | Cytoplasm | Phosphatase | |||||
| MEOX1 | Mesenchyme homeobox 1 | Nucleus | Transcription factor | |||||
| MEOX2 | Mesenchyme homeobox 2 | Nucleus | Transcription factor | |||||
| MYF5/6 | Myogenic factor 6 (herculin) | Nucleus | Transcription factor | |||||
| MYOD1 | Myogenic differentiation 1 | Nucleus | Transcription factor | |||||
| PRRX1 | Paired related homeobox 1 | Nucleus | Transcription factor | |||||
| Other potential targets | ||||||||
| ABAT | 4-Aminobutyrate aminotransferase | Cytoplasm | Enzyme | Valproic acid | ||||
| ADRA1D | Adrenergic, α-1D-, receptor | Plasma membrane | GPCR | Paliperidone, risperidone, antazoline, acetaminophen, epinephrine, acetaminophen | ||||
| ADRA2A | Adrenergic, α-2A-, receptor | Plasma membrane | ||||||
| ADRA2C | Adrenergic, α-2C-, receptor | Plasma membrane | ||||||
| DHFR | Dihydrofolate reductase | Unknown | Enzyme | Pyrimethamine, trimethoprim, iclaprim, methotrexate | ||||
| (B) Verification of PAX3-FKHR binding site via enhancer assay | ||||||||
| Gene | Enhancer no. | Binding intensity | Fold induction by activators | Rel. Location | Dist. Tx Start bp | Dist. Tx End bp | ||
| None | PAX3 | PAX3-FKHR | ||||||
| Vector | None | NA | 1.0 | 1.0 | 0.9 | NA | NA | NA |
| ALK | 1 | High | 2.6 | 10.8 | 19.5 | 3rd Intron | −262,835 | 464,601 |
| FGFR4 | 1 | Low | 1.5 | 1.9 | 3.7 | 3′ downstream | −8,913 | −839 |
| FGFR4 | 2 | High | 1.9 | 5.7 | 8.3 | 3′ downstream | −16,273 | −8,199 |
| IGF1R | 1 | Med | 1.8 | 4.0 | 4.8 | 2nd Intron | −136,375 | 171,486 |
| MET | 1 | Low | 3.9 | 10.2 | 7.4 | 3rd Intron | −35,329 | 61,711 |
| MET | 2 | High | 1.3 | 2.5 | 3.8 | 18th Intron | −83,277 | 13,763 |
| MYCN | 1 | Med | 0.9 | 3.8 | 5.4 | 3′ downstream | −96,819 | −92,786 |
| MEOX1 | 1 | Med | 1.2 | 2.4 | 5.4 | 5′ upstream | 994 | 20,274 |
| MEOX2 | 1 | High | 0.8 | 0.8 | 3.8 | 1 intron | −798 | 73,218 |
| PRRX1 | 1 | Med | 0.6 | 2.1 | 18.2 | 1st intron | −4,226 | 67,742 |