The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin

Sean Bong Lee; Karen Huang; Rachel Palmer; Vivi B. Truong; Doris Herzlinger; Kathryn A. Kolquist; Jenise Wong; Charles Paulding; Seung Kew Yoon; William Gerald; Jonathan D. Oliner; Daniel A. Haber

doi:10.1016/S0092-8674(00)80053-7

The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin

Sean Bong Lee
, Karen Huang
, Rachel Palmer
, Vivi B. Truong
, Doris Herzlinger
, Kathryn A. Kolquist
, Jenise Wong
, Charles Paulding
, Seung Kew Yoon
, William Gerald
, Jonathan D. Oliner
, Daniel A. Haber

Division of Gastroenterology

Harvard University
Thermo Fisher Scientific, Inc.
Cornell University
Memorial Sloan-Kettering Cancer Center
Amgen Incorporated

Research output: Contribution to journal › Article › peer-review

267 Scopus citations

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.

Original language	English
Pages (from-to)	663-673
Number of pages	11
Journal	Cell
Volume	98
Issue number	5
DOIs	https://doi.org/10.1016/S0092-8674(00)80053-7
State	Published - 3 Sep 1999

Bibliographical note

Funding Information:
We thank Drs. P. Reynolds and W. Hong for helpful discussions; Drs. N. Dyson and J. Settleman for critical review of this manuscript; and Drs. G. Johnson, T. Wang, J. Kreidberg, N. Luetteke, and D. Lee for providing important reagents. This work was supported by National Institutes of Health grants CA71167 (to S. B. L.) and CA58596 (to D. A. H.). K. H. is an HHMI Predoctoral Fellow.

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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.",

author = "Lee, \{Sean Bong\} and Karen Huang and Rachel Palmer and Truong, \{Vivi B.\} and Doris Herzlinger and Kolquist, \{Kathryn A.\} and Jenise Wong and Charles Paulding and Yoon, \{Seung Kew\} and William Gerald and Oliner, \{Jonathan D.\} and Haber, \{Daniel A.\}",

note = "Funding Information: We thank Drs. P. Reynolds and W. Hong for helpful discussions; Drs. N. Dyson and J. Settleman for critical review of this manuscript; and Drs. G. Johnson, T. Wang, J. Kreidberg, N. Luetteke, and D. Lee for providing important reagents. This work was supported by National Institutes of Health grants CA71167 (to S. B. L.) and CA58596 (to D. A. H.). K. H. is an HHMI Predoctoral Fellow.",

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doi = "10.1016/S0092-8674(00)80053-7",

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T1 - The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin

AU - Lee, Sean Bong

AU - Huang, Karen

AU - Palmer, Rachel

AU - Truong, Vivi B.

AU - Herzlinger, Doris

AU - Kolquist, Kathryn A.

AU - Wong, Jenise

AU - Paulding, Charles

AU - Yoon, Seung Kew

AU - Gerald, William

AU - Oliner, Jonathan D.

AU - Haber, Daniel A.

N1 - Funding Information: We thank Drs. P. Reynolds and W. Hong for helpful discussions; Drs. N. Dyson and J. Settleman for critical review of this manuscript; and Drs. G. Johnson, T. Wang, J. Kreidberg, N. Luetteke, and D. Lee for providing important reagents. This work was supported by National Institutes of Health grants CA71167 (to S. B. L.) and CA58596 (to D. A. H.). K. H. is an HHMI Predoctoral Fellow.

PY - 1999/9/3

Y1 - 1999/9/3

N2 - 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.

AB - 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.

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DO - 10.1016/S0092-8674(00)80053-7

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VL - 98

SP - 663

EP - 673

JO - Cell

JF - Cell

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ER -

The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin

Abstract

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