Cargando…

Stat3 activation in human endometrial and cervical cancers

The activation of signal transducer and activator of transcription 3 (Stat3) has been implicated in the oncogenesis of cancer and is regarded as a novel target for cancer therapy. Stat3 is classified as a proto-oncogene, because an activated form of Stat3 can mediate oncogenic transformation in cult...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, C-L, Hsieh, F-C, Lieblein, J C, Brown, J, Chan, C, Wallace, J A, Cheng, G, Hall, B M, Lin, J
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360038/
https://www.ncbi.nlm.nih.gov/pubmed/17311011
http://dx.doi.org/10.1038/sj.bjc.6603597
_version_ 1782152948894138368
author Chen, C-L
Hsieh, F-C
Lieblein, J C
Brown, J
Chan, C
Wallace, J A
Cheng, G
Hall, B M
Lin, J
author_facet Chen, C-L
Hsieh, F-C
Lieblein, J C
Brown, J
Chan, C
Wallace, J A
Cheng, G
Hall, B M
Lin, J
author_sort Chen, C-L
collection PubMed
description The activation of signal transducer and activator of transcription 3 (Stat3) has been implicated in the oncogenesis of cancer and is regarded as a novel target for cancer therapy. Stat3 is classified as a proto-oncogene, because an activated form of Stat3 can mediate oncogenic transformation in cultured cells and tumour formation in nude mice. The constitutive activation of Stat3 has been frequently detected in various types of human cancers. However, the constitutive activation of Stat3 in endometrial and cervical cancers has not been studied. We examined tyrosine phosphorylation of Stat3 (activated form of Stat3) in multiple endometrial and cervical cancer tissues using tissue microarray slides as well as cancer cell lines to explore the possible activation of Stat3. Our results indicated that elevated phosphorylation of Stat3 was detected in cervical and endometrial cancer cell lines. Our results also showed that elevated levels of phosphorylation of Stat3 protein were detected in the endometrial and cervical cancer specimens. This is the first study to demonstrate that Stat3 is activated in human endometrial and cervical cancer tissues. Immunohistochemical staining showed that activated Stat3 is associated with increased expression of downstream antiapoptotic genes, Bcl-xL, survivin, and Mcl-1 in these tissues. Expression of a dominant-negative Stat3 mutant using adenovirus-mediated gene transfer inhibited cell growth and induced apoptosis in HeLa and SiHa cervical cancer cell lines expressing elevated levels of Stat3 phosphorylation. Further, a JAK/Stat3 small molecular inhibitor, JSI-124, induced apoptosis more selectively in HeLa and SiHa cancer cell lines than Ishikawa cell line without elevated levels of Stat3 phosphorylation. These results indicate that Stat3 is activated in human endometrial and cervical cancers and the inhibition of constitutive Stat3 signaling may be an effective target for cancer intervention in these two cancers.
format Text
id pubmed-2360038
institution National Center for Biotechnology Information
language English
publishDate 2007
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-23600382009-09-10 Stat3 activation in human endometrial and cervical cancers Chen, C-L Hsieh, F-C Lieblein, J C Brown, J Chan, C Wallace, J A Cheng, G Hall, B M Lin, J Br J Cancer Translational Therapeutics The activation of signal transducer and activator of transcription 3 (Stat3) has been implicated in the oncogenesis of cancer and is regarded as a novel target for cancer therapy. Stat3 is classified as a proto-oncogene, because an activated form of Stat3 can mediate oncogenic transformation in cultured cells and tumour formation in nude mice. The constitutive activation of Stat3 has been frequently detected in various types of human cancers. However, the constitutive activation of Stat3 in endometrial and cervical cancers has not been studied. We examined tyrosine phosphorylation of Stat3 (activated form of Stat3) in multiple endometrial and cervical cancer tissues using tissue microarray slides as well as cancer cell lines to explore the possible activation of Stat3. Our results indicated that elevated phosphorylation of Stat3 was detected in cervical and endometrial cancer cell lines. Our results also showed that elevated levels of phosphorylation of Stat3 protein were detected in the endometrial and cervical cancer specimens. This is the first study to demonstrate that Stat3 is activated in human endometrial and cervical cancer tissues. Immunohistochemical staining showed that activated Stat3 is associated with increased expression of downstream antiapoptotic genes, Bcl-xL, survivin, and Mcl-1 in these tissues. Expression of a dominant-negative Stat3 mutant using adenovirus-mediated gene transfer inhibited cell growth and induced apoptosis in HeLa and SiHa cervical cancer cell lines expressing elevated levels of Stat3 phosphorylation. Further, a JAK/Stat3 small molecular inhibitor, JSI-124, induced apoptosis more selectively in HeLa and SiHa cancer cell lines than Ishikawa cell line without elevated levels of Stat3 phosphorylation. These results indicate that Stat3 is activated in human endometrial and cervical cancers and the inhibition of constitutive Stat3 signaling may be an effective target for cancer intervention in these two cancers. Nature Publishing Group 2007-02-26 2007-02-20 /pmc/articles/PMC2360038/ /pubmed/17311011 http://dx.doi.org/10.1038/sj.bjc.6603597 Text en Copyright © 2007 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Translational Therapeutics
Chen, C-L
Hsieh, F-C
Lieblein, J C
Brown, J
Chan, C
Wallace, J A
Cheng, G
Hall, B M
Lin, J
Stat3 activation in human endometrial and cervical cancers
title Stat3 activation in human endometrial and cervical cancers
title_full Stat3 activation in human endometrial and cervical cancers
title_fullStr Stat3 activation in human endometrial and cervical cancers
title_full_unstemmed Stat3 activation in human endometrial and cervical cancers
title_short Stat3 activation in human endometrial and cervical cancers
title_sort stat3 activation in human endometrial and cervical cancers
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360038/
https://www.ncbi.nlm.nih.gov/pubmed/17311011
http://dx.doi.org/10.1038/sj.bjc.6603597
work_keys_str_mv AT chencl stat3activationinhumanendometrialandcervicalcancers
AT hsiehfc stat3activationinhumanendometrialandcervicalcancers
AT liebleinjc stat3activationinhumanendometrialandcervicalcancers
AT brownj stat3activationinhumanendometrialandcervicalcancers
AT chanc stat3activationinhumanendometrialandcervicalcancers
AT wallaceja stat3activationinhumanendometrialandcervicalcancers
AT chengg stat3activationinhumanendometrialandcervicalcancers
AT hallbm stat3activationinhumanendometrialandcervicalcancers
AT linj stat3activationinhumanendometrialandcervicalcancers