Advanced

Constitutive expression of the Wilms' tumor gene (WT1) in the leukemic cell line U937 blocks parts of the differentiation program

Svedberg, Helena LU ; Chylicki, Kristina; Baldetorp, Bo LU ; Rauscher, F J 3rd and Gullberg, Urban LU (1998) In Oncogene 16(7). p.925-932
Abstract
The Wilms tumor gene, WT1, encodes a zinc-finger DNA binding protein which is thought to function as a tissue specific transcription factor, regulating cell growth and differentiation. High expression of WT1 has been detected in a range of acute leukemias. To elucidate a role for WT1 in leukemogenesis, we transfected the monoblastic cell line U937, which lacks detectable levels of endogenous WT1, with two isoforms of WT1. We showed that, in contrast to U937 control cells, cells constitutively expressing either of the isoforms, WT1(-KTS) or WT1(+KTS), did not respond to differentiation induction by retinoic acid or vitamin D3, as judged by the capacity to reduce nitro blue tetrazolium and morphology. Although U937 cells expressing WT1 were... (More)
The Wilms tumor gene, WT1, encodes a zinc-finger DNA binding protein which is thought to function as a tissue specific transcription factor, regulating cell growth and differentiation. High expression of WT1 has been detected in a range of acute leukemias. To elucidate a role for WT1 in leukemogenesis, we transfected the monoblastic cell line U937, which lacks detectable levels of endogenous WT1, with two isoforms of WT1. We showed that, in contrast to U937 control cells, cells constitutively expressing either of the isoforms, WT1(-KTS) or WT1(+KTS), did not respond to differentiation induction by retinoic acid or vitamin D3, as judged by the capacity to reduce nitro blue tetrazolium and morphology. Although U937 cells expressing WT1 were hampered in their ability to differentiate on incubation with retinoic acid and vitamin D3, the induced G1/G0-accumulation was similar to differentiating control cells treated with inducers. Furthermore, distinct effects on the maturation process were indicated by downregulation of the myeloid cell surface makers CD13 and CD15, while the upregulation of CD14 and CD11c on WT1 transfected cells was similar to control cells upon incubation with retinoic acid and vitamin D3. Taken together our results demonstrate that a constitutive expression of WT1 in the leukemic cell line U937 leads to impairment of differentiation responses, indicating that a high expression of WT1 can contribute to the differentiation block of acute leukemia. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
WT1, leukemia, differentiation, hematopoiesis, U937
in
Oncogene
volume
16
issue
7
pages
925 - 932
publisher
Nature Publishing Group
external identifiers
  • pmid:9484784
  • scopus:0032545941
ISSN
1476-5594
DOI
10.1038/sj.onc.1201613
language
English
LU publication?
yes
id
a49a988a-2f0e-4c3e-b711-39a28f11f5be (old id 1112817)
date added to LUP
2008-07-11 11:47:31
date last changed
2017-01-22 03:23:03
@article{a49a988a-2f0e-4c3e-b711-39a28f11f5be,
  abstract     = {The Wilms tumor gene, WT1, encodes a zinc-finger DNA binding protein which is thought to function as a tissue specific transcription factor, regulating cell growth and differentiation. High expression of WT1 has been detected in a range of acute leukemias. To elucidate a role for WT1 in leukemogenesis, we transfected the monoblastic cell line U937, which lacks detectable levels of endogenous WT1, with two isoforms of WT1. We showed that, in contrast to U937 control cells, cells constitutively expressing either of the isoforms, WT1(-KTS) or WT1(+KTS), did not respond to differentiation induction by retinoic acid or vitamin D3, as judged by the capacity to reduce nitro blue tetrazolium and morphology. Although U937 cells expressing WT1 were hampered in their ability to differentiate on incubation with retinoic acid and vitamin D3, the induced G1/G0-accumulation was similar to differentiating control cells treated with inducers. Furthermore, distinct effects on the maturation process were indicated by downregulation of the myeloid cell surface makers CD13 and CD15, while the upregulation of CD14 and CD11c on WT1 transfected cells was similar to control cells upon incubation with retinoic acid and vitamin D3. Taken together our results demonstrate that a constitutive expression of WT1 in the leukemic cell line U937 leads to impairment of differentiation responses, indicating that a high expression of WT1 can contribute to the differentiation block of acute leukemia.},
  author       = {Svedberg, Helena and Chylicki, Kristina and Baldetorp, Bo and Rauscher, F J 3rd and Gullberg, Urban},
  issn         = {1476-5594},
  keyword      = {WT1,leukemia,differentiation,hematopoiesis,U937},
  language     = {eng},
  number       = {7},
  pages        = {925--932},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {Constitutive expression of the Wilms' tumor gene (WT1) in the leukemic cell line U937 blocks parts of the differentiation program},
  url          = {http://dx.doi.org/10.1038/sj.onc.1201613},
  volume       = {16},
  year         = {1998},
}