TY - JOUR
T1 - STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes.
AU - Zhang, Qian
AU - Wang, Hong Y.
AU - Marzec, Michal
AU - Raghunath, Puthiyaveettil N.
AU - Nagasawa, Tomohiko
AU - Wasik, Mariusz A.
N1 - M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved.
CAPLUS AN 2005:446404(Journal)
PY - 2005
Y1 - 2005
N2 - 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)]
AB - 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)]
KW - gene silencing STAT3 DNA methyltransferase SHP1 lymphoma
KW - histone diacetylase STAT3 SHP1 methylation lymphoma
U2 - 10.1073/pnas.0501959102
DO - 10.1073/pnas.0501959102
M3 - Journal article
VL - 102
SP - 6948
EP - 6953
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 19
ER -