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Stat3 Mediates Expression of Autotaxin in Breast Cancer

We determined that signal transducer and activator of transcription 3 (Stat3) is tyrosine phosphorylated in 37% of primary breast tumors and 63% of paired metastatic axillary lymph nodes. Examination of the distribution of tyrosine phosphorylated (pStat3) in primary tumors revealed heterogenous expr...

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Autores principales: Azare, Janeen, Doane, Ashley, Leslie, Kenneth, Chang, Qing, Berishaj, Marjan, Nnoli, Jennifer, Mark, Kevin, Al-Ahmadie, Hikmat, Gerald, William, Hassimi, Maryam, Viale, Agnes, Stracke, Mary, Lyden, David, Bromberg, Jacqueline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225372/
https://www.ncbi.nlm.nih.gov/pubmed/22140473
http://dx.doi.org/10.1371/journal.pone.0027851
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author Azare, Janeen
Doane, Ashley
Leslie, Kenneth
Chang, Qing
Berishaj, Marjan
Nnoli, Jennifer
Mark, Kevin
Al-Ahmadie, Hikmat
Gerald, William
Hassimi, Maryam
Viale, Agnes
Stracke, Mary
Lyden, David
Bromberg, Jacqueline
author_facet Azare, Janeen
Doane, Ashley
Leslie, Kenneth
Chang, Qing
Berishaj, Marjan
Nnoli, Jennifer
Mark, Kevin
Al-Ahmadie, Hikmat
Gerald, William
Hassimi, Maryam
Viale, Agnes
Stracke, Mary
Lyden, David
Bromberg, Jacqueline
author_sort Azare, Janeen
collection PubMed
description We determined that signal transducer and activator of transcription 3 (Stat3) is tyrosine phosphorylated in 37% of primary breast tumors and 63% of paired metastatic axillary lymph nodes. Examination of the distribution of tyrosine phosphorylated (pStat3) in primary tumors revealed heterogenous expression within the tumor with the highest levels found in cells on the edge of tumors with relatively lower levels in the central portion of tumors. In order to determine Stat3 target genes that may be involved in migration and metastasis, we identified those genes that were differentially expressed in primary breast cancer samples as a function of pStat3 levels. In addition to known Stat3 transcriptional targets (Twist, Snail, Tenascin-C and IL-8), we identified ENPP2 as a novel Stat3 regulated gene, which encodes autotaxin (ATX), a secreted lysophospholipase which mediates mammary tumorigenesis and cancer cell migration. A positive correlation between nuclear pStat3 and ATX was determined by immunohistochemical analysis of primary breast cancer samples and matched axillary lymph nodes and in several breast cancer derived cell lines. Inhibition of pStat3 or reducing Stat3 expression led to a decrease in ATX levels and cell migration. An association between Stat3 and the ATX promoter, which contains a number of putative Stat3 binding sites, was determined by chromatin immunoprecipitation. These observations suggest that activated Stat3 may regulate the migration of breast cancer cells through the regulation of ATX.
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spelling pubmed-32253722011-12-02 Stat3 Mediates Expression of Autotaxin in Breast Cancer Azare, Janeen Doane, Ashley Leslie, Kenneth Chang, Qing Berishaj, Marjan Nnoli, Jennifer Mark, Kevin Al-Ahmadie, Hikmat Gerald, William Hassimi, Maryam Viale, Agnes Stracke, Mary Lyden, David Bromberg, Jacqueline PLoS One Research Article We determined that signal transducer and activator of transcription 3 (Stat3) is tyrosine phosphorylated in 37% of primary breast tumors and 63% of paired metastatic axillary lymph nodes. Examination of the distribution of tyrosine phosphorylated (pStat3) in primary tumors revealed heterogenous expression within the tumor with the highest levels found in cells on the edge of tumors with relatively lower levels in the central portion of tumors. In order to determine Stat3 target genes that may be involved in migration and metastasis, we identified those genes that were differentially expressed in primary breast cancer samples as a function of pStat3 levels. In addition to known Stat3 transcriptional targets (Twist, Snail, Tenascin-C and IL-8), we identified ENPP2 as a novel Stat3 regulated gene, which encodes autotaxin (ATX), a secreted lysophospholipase which mediates mammary tumorigenesis and cancer cell migration. A positive correlation between nuclear pStat3 and ATX was determined by immunohistochemical analysis of primary breast cancer samples and matched axillary lymph nodes and in several breast cancer derived cell lines. Inhibition of pStat3 or reducing Stat3 expression led to a decrease in ATX levels and cell migration. An association between Stat3 and the ATX promoter, which contains a number of putative Stat3 binding sites, was determined by chromatin immunoprecipitation. These observations suggest that activated Stat3 may regulate the migration of breast cancer cells through the regulation of ATX. Public Library of Science 2011-11-28 /pmc/articles/PMC3225372/ /pubmed/22140473 http://dx.doi.org/10.1371/journal.pone.0027851 Text en Azare et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Azare, Janeen
Doane, Ashley
Leslie, Kenneth
Chang, Qing
Berishaj, Marjan
Nnoli, Jennifer
Mark, Kevin
Al-Ahmadie, Hikmat
Gerald, William
Hassimi, Maryam
Viale, Agnes
Stracke, Mary
Lyden, David
Bromberg, Jacqueline
Stat3 Mediates Expression of Autotaxin in Breast Cancer
title Stat3 Mediates Expression of Autotaxin in Breast Cancer
title_full Stat3 Mediates Expression of Autotaxin in Breast Cancer
title_fullStr Stat3 Mediates Expression of Autotaxin in Breast Cancer
title_full_unstemmed Stat3 Mediates Expression of Autotaxin in Breast Cancer
title_short Stat3 Mediates Expression of Autotaxin in Breast Cancer
title_sort stat3 mediates expression of autotaxin in breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225372/
https://www.ncbi.nlm.nih.gov/pubmed/22140473
http://dx.doi.org/10.1371/journal.pone.0027851
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