The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin Journal Article
| Authors: | Lee, S. B.; Huang, K.; Palmer, R.; Truong, V. B.; Herzlinger, D.; Kolquist, K. A.; Wong, J.; Paulding, C.; Yoon, S. K.; Gerald, W.; Oliner, J. D.; Haber, D. A. |
| Article Title: | The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin |
| Abstract: | WT1 encodes a zinc finger transcription factor implicated in kidney differentiation and tumorigenesis. In reporter assays, WT1 represses transcription from GC- and TC-rich promoters, but its physiological targets remain uncertain. We used hybridization to high-density oligonucleotide arrays to search for native genes whose expression is altered following inducible expression of WT1. The major target of WT1 was amphiregulin, a member of the epidermal growth factor family. The WT1(-KTS) isoform binds directly to the amphiregulin promoter, resulting in potent transcriptional activation. The in vivo expression profile of amphiregulin during fetal kidney development mirrors the highly specific pattern of WT1 itself, and recombinant Amphiregulin stimulates epithelial branching in organ cultures of embryonic mouse kidney. These observations suggest a model for WT1 as a transcriptional regulator during kidney differentiation. |
| Keywords: | osteosarcoma; protein expression; intercellular signaling peptides and proteins; dna-binding proteins; nonhuman; mouse; animals; mice; animal tissue; gene expression; transcription initiation; animal experiment; transcription factor; dose-response relationship, drug; tumor cells, cultured; time factors; animalia; transcription factors; tumor suppressor gene; gene activation; kidney; transcription regulation; molecular sequence data; rna, messenger; oligonucleotide array sequence analysis; protein induction; base sequence; models, genetic; response elements; gene induction; ureter; oligonucleotide; glycoproteins; mutagenesis; tissue differentiation; amphiregulin; nephroblastoma; kidney development; growth substances; wt1 proteins; dna footprinting; promoter regions (genetics); trans-activation (genetics); humans; priority journal; article |
| Journal Title: | Cell |
| Volume: | 98 |
| Issue: | 5 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 1999-09-03 |
| Start Page: | 663 |
| End Page: | 673 |
| Language: | English |
| DOI: | 10.1016/s0092-8674(00)80053-7 |
| PUBMED: | 10490105 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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