STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes.

Research output: Contribution to journalJournal articleResearchpeer-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 languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number19
Pages (from-to)6948-6953
Number of pages6
Publication statusPublished - 2005
Externally publishedYes

Bibliographical note

M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved.

CAPLUS AN 2005:446404(Journal)

    Research areas

  • gene silencing STAT3 DNA methyltransferase SHP1 lymphoma, histone diacetylase STAT3 SHP1 methylation lymphoma

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