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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...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2007
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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 |
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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 |
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