The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin.
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.
Lee
S B
SB
Laboratory of Molecular Genetics, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown 02129, USA.
Huang
K
K
Palmer
R
R
Truong
V B
VB
Herzlinger
D
D
Kolquist
K A
KA
Wong
J
J
Paulding
C
C
Yoon
S K
SK
Gerald
W
W
Oliner
J D
JD
Haber
D A
DA
D066258:Amphiregulin; D000818:Animals; D001483:Base Sequence; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066255:EGF Family of Proteins; D006023:Glycoproteins / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D006133:Growth Substances / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000033:anatomy & histology / Q000196:embryology; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D020218:Response Elements / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014513:Ureter / Q000196:embryology; D025721:WT1 Proteins
C587848:AREG protein, human; D066258:Amphiregulin; C587849:Areg protein, mouse; D004268:DNA-Binding Proteins; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025721:WT1 Proteins