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

Qian Zhang; Hong Y. Wang; Michal Marzec; Puthiyaveettil N. Raghunath; Tomohiko Nagasawa; Mariusz A. Wasik

doi:10.1073/pnas.0501959102

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

Qian Zhang, Hong Y. Wang, Michal Marzec, Puthiyaveettil N. Raghunath, Tomohiko Nagasawa, Mariusz A. Wasik

193 Citationer (Scopus)

Abstract

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)]

Originalsprog	Engelsk
Tidsskrift	Proceedings of the National Academy of Sciences of the United States of America
Vol/bind	102
Udgave nummer	19
Sider (fra-til)	6948-6953
Antal sider	6
ISSN	0027-8424
DOI	https://doi.org/10.1073/pnas.0501959102
Status	Udgivet - 2005
Udgivet eksternt	Ja

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10.1073/pnas.0501959102

Citationsformater

Zhang, Q., Wang, H. Y., Marzec, M., Raghunath, P. N., Nagasawa, T., & Wasik, M. A. (2005). STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America, 102(19), 6948-6953. https://doi.org/10.1073/pnas.0501959102

STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes. / Zhang, Qian; Wang, Hong Y.; Marzec, Michal et al.

I: Proceedings of the National Academy of Sciences of the United States of America, Bind 102, Nr. 19, 2005, s. 6948-6953.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Zhang, Q, Wang, HY, Marzec, M, Raghunath, PN, Nagasawa, T & Wasik, MA 2005, 'STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes.', Proceedings of the National Academy of Sciences of the United States of America, bind 102, nr. 19, s. 6948-6953. https://doi.org/10.1073/pnas.0501959102

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

abstract = "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)]",

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author = "Qian Zhang and Wang, {Hong Y.} and Michal Marzec and Raghunath, {Puthiyaveettil N.} and Tomohiko Nagasawa and Wasik, {Mariusz A.}",

year = "2005",

doi = "10.1073/pnas.0501959102",

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AU - Zhang, Qian

AU - Wang, Hong Y.

AU - Marzec, Michal

AU - Raghunath, Puthiyaveettil N.

AU - Nagasawa, Tomohiko

AU - Wasik, Mariusz A.

PY - 2005

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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

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DO - 10.1073/pnas.0501959102

M3 - Journal article

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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

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ER -

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

Abstract

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