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WT1-mediated repression of the proapoptotic transcription factor ZNF224 is triggered by the BCR-ABL oncogene.

Montano, Giorgia LU ; Vidovic, Karina LU ; Palladino, Chiara; Cesaro, Elena; Sodaro, Gaetano; Quintarelli, Concetta; De Angelis, Biagio; Errichiello, Santa; Pane, Fabrizio and Izzo, Paola, et al. (2015) In Oncotarget 29(6). p.37-28223
Abstract
The Kruppel-like protein ZNF224 is a co-factor of the Wilms' tumor 1 protein, WT1. We have previously shown that ZNF224 exerts a specific proapoptotic role in chronic myelogenous leukemia (CML) K562 cells and contributes to cytosine arabinoside-induced apoptosis, by modulating WT1-dependent transcription of apoptotic genes. Here we demonstrate that ZNF224 gene expression is down-regulated both in BCR-ABL positive cell lines and in primary CML samples and is restored after imatinib and second generation tyrosine kinase inhibitors treatment. We also show that WT1, whose expression is positively regulated by BCR-ABL, represses transcription of the ZNF224 gene. Finally, we report that ZNF224 is significantly down-regulated in patients with... (More)
The Kruppel-like protein ZNF224 is a co-factor of the Wilms' tumor 1 protein, WT1. We have previously shown that ZNF224 exerts a specific proapoptotic role in chronic myelogenous leukemia (CML) K562 cells and contributes to cytosine arabinoside-induced apoptosis, by modulating WT1-dependent transcription of apoptotic genes. Here we demonstrate that ZNF224 gene expression is down-regulated both in BCR-ABL positive cell lines and in primary CML samples and is restored after imatinib and second generation tyrosine kinase inhibitors treatment. We also show that WT1, whose expression is positively regulated by BCR-ABL, represses transcription of the ZNF224 gene. Finally, we report that ZNF224 is significantly down-regulated in patients with BCR-ABL positive chronic phase-CML showing poor response or resistance to imatinib treatment as compared to high-responder patients. Taken as a whole, our data disclose a novel pathway activated by BCR-ABL that leads to inhibition of apoptosis through the ZNF224 repression. ZNF224 could thus represent a novel promising therapeutic target in CML. (Less)
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Contribution to journal
publication status
published
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Oncotarget
volume
29
issue
6
pages
37 - 28223
publisher
Impact Journals, LLC
external identifiers
  • pmid:26320177
  • wos:000363161300131
  • scopus:84944463075
ISSN
1949-2553
DOI
10.18632/oncotarget.4950
language
English
LU publication?
yes
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a215f04f-eabe-495a-8d1c-78ce55b0495e (old id 8043711)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26320177?dopt=Abstract
date added to LUP
2015-10-08 17:39:55
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2017-07-02 03:56:30
@article{a215f04f-eabe-495a-8d1c-78ce55b0495e,
  abstract     = {The Kruppel-like protein ZNF224 is a co-factor of the Wilms' tumor 1 protein, WT1. We have previously shown that ZNF224 exerts a specific proapoptotic role in chronic myelogenous leukemia (CML) K562 cells and contributes to cytosine arabinoside-induced apoptosis, by modulating WT1-dependent transcription of apoptotic genes. Here we demonstrate that ZNF224 gene expression is down-regulated both in BCR-ABL positive cell lines and in primary CML samples and is restored after imatinib and second generation tyrosine kinase inhibitors treatment. We also show that WT1, whose expression is positively regulated by BCR-ABL, represses transcription of the ZNF224 gene. Finally, we report that ZNF224 is significantly down-regulated in patients with BCR-ABL positive chronic phase-CML showing poor response or resistance to imatinib treatment as compared to high-responder patients. Taken as a whole, our data disclose a novel pathway activated by BCR-ABL that leads to inhibition of apoptosis through the ZNF224 repression. ZNF224 could thus represent a novel promising therapeutic target in CML.},
  author       = {Montano, Giorgia and Vidovic, Karina and Palladino, Chiara and Cesaro, Elena and Sodaro, Gaetano and Quintarelli, Concetta and De Angelis, Biagio and Errichiello, Santa and Pane, Fabrizio and Izzo, Paola and Grosso, Michela and Gullberg, Urban and Costanzo, Paola},
  issn         = {1949-2553},
  language     = {eng},
  number       = {6},
  pages        = {37--28223},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {WT1-mediated repression of the proapoptotic transcription factor ZNF224 is triggered by the BCR-ABL oncogene.},
  url          = {http://dx.doi.org/10.18632/oncotarget.4950},
  volume       = {29},
  year         = {2015},
}