STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes.
Research output: Contribution to journal › Journal article › Research › peer-review
Expression of SHP-1 phosphatase, a key neg. regulator of cell signaling, is lost in T cell lymphomas and other malignancies due to DNA methylation of the SHP-1 promoter by a currently undefined mechanism. The authors demonstrate that malignant T cells express DNA methyltransferase (DNMT) 1 and that constantly activated signal transducer and activator of transcription (STAT) 3 is capable of binding in vitro to DNA oligonucleotides corresponding to 4 STAT3 SIE/GAS binding sites identified in the SHP-1 promoter. STAT3, DNMT1, and histone deacetylase 1 form complexes and bind to the SHP-1 promoter in vivo. Treatment with pharmacol. grade DNMT1 anti-sense oligonucleotides and STAT3 small-interfering RNA induces in the malignant T cells DNA demethylation and expression of SHP-1 gene. These data indicate that STAT3 may, in part, transform cells by inducing epigenetic silencing of SHP-1 in cooperation with DNMT1 and, apparently, histone deacetylase 1. Reversal of such gene silencing represents an attractive aim for novel anticancer therapies. [on SciFinder(R)]
Original language | English |
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Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 102 |
Issue number | 19 |
Pages (from-to) | 6948-6953 |
Number of pages | 6 |
ISSN | 0027-8424 |
DOIs | |
Publication status | Published - 2005 |
Externally published | Yes |
Bibliographical note
M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved.
CAPLUS AN 2005:446404(Journal)
- gene silencing STAT3 DNA methyltransferase SHP1 lymphoma, histone diacetylase STAT3 SHP1 methylation lymphoma
Research areas
ID: 202376345