Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling

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Introduction: It has been demonstrated that leukemia inhibitory factor (LIF) induces epithelium apoptosis through Stat3 activation during mouse mammary gland involution. In contrast, it has been shown that this transcription factor is commonly activated in breast cancer cells, although what causes t...

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Autores principales:	Quaglino, A., Schere-Levy, C., Romorini, L., Meiss, R.P., Kordon, E.C.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2007
Materias:	2 (2 amino 3 methoxyphenyl)chromone crystal violet leukemia inhibitory factor mitogen activated protein kinase 1 mitogen activated protein kinase 3 protein antibody STAT3 protein leukemia inhibitory factor receptor alpha Lif protein, mouse Lifr protein, mouse messenger RNA Stat3 protein, mouse tyrosine unclassified drug animal cell animal experiment animal model article breast tumor cell survival female human human cell immunohistochemistry mouse nonhuman phosphorylation protein analysis protein expression protein function reverse transcription polymerase chain reaction Western blotting animal Bagg albino mouse cell culture experimental neoplasm fluorescent antibody technique genetics immunoprecipitation metabolism pathology signal transduction Animals Blotting, Western Cell Survival Female Fluorescent Antibody Technique Immunoprecipitation Leukemia Inhibitory Factor Leukemia Inhibitory Factor Receptor alpha Subunit Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Phosphorylation Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction STAT3 Transcription Factor Tumor Cells, Cultured Tyrosine
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_14655411_v9_n5_p_Quaglino
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paperaa:paper_14655411_v9_n5_p_Quaglino
record_format	dspace
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	2 (2 amino 3 methoxyphenyl)chromone crystal violet leukemia inhibitory factor mitogen activated protein kinase 1 mitogen activated protein kinase 3 protein antibody STAT3 protein leukemia inhibitory factor leukemia inhibitory factor receptor alpha Lif protein, mouse Lifr protein, mouse messenger RNA mitogen activated protein kinase 1 mitogen activated protein kinase 3 STAT3 protein Stat3 protein, mouse tyrosine unclassified drug animal cell animal experiment animal model article breast tumor cell survival female human human cell immunohistochemistry mouse nonhuman phosphorylation protein analysis protein expression protein function reverse transcription polymerase chain reaction Western blotting animal Bagg albino mouse cell culture experimental neoplasm fluorescent antibody technique genetics immunoprecipitation metabolism pathology signal transduction Animals Blotting, Western Cell Survival Female Fluorescent Antibody Technique Immunoprecipitation Leukemia Inhibitory Factor Leukemia Inhibitory Factor Receptor alpha Subunit Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Phosphorylation Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction STAT3 Transcription Factor Tumor Cells, Cultured Tyrosine
spellingShingle	2 (2 amino 3 methoxyphenyl)chromone crystal violet leukemia inhibitory factor mitogen activated protein kinase 1 mitogen activated protein kinase 3 protein antibody STAT3 protein leukemia inhibitory factor leukemia inhibitory factor receptor alpha Lif protein, mouse Lifr protein, mouse messenger RNA mitogen activated protein kinase 1 mitogen activated protein kinase 3 STAT3 protein Stat3 protein, mouse tyrosine unclassified drug animal cell animal experiment animal model article breast tumor cell survival female human human cell immunohistochemistry mouse nonhuman phosphorylation protein analysis protein expression protein function reverse transcription polymerase chain reaction Western blotting animal Bagg albino mouse cell culture experimental neoplasm fluorescent antibody technique genetics immunoprecipitation metabolism pathology signal transduction Animals Blotting, Western Cell Survival Female Fluorescent Antibody Technique Immunoprecipitation Leukemia Inhibitory Factor Leukemia Inhibitory Factor Receptor alpha Subunit Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Phosphorylation Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction STAT3 Transcription Factor Tumor Cells, Cultured Tyrosine Quaglino, A. Schere-Levy, C. Romorini, L. Meiss, R.P. Kordon, E.C. Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling
topic_facet	2 (2 amino 3 methoxyphenyl)chromone crystal violet leukemia inhibitory factor mitogen activated protein kinase 1 mitogen activated protein kinase 3 protein antibody STAT3 protein leukemia inhibitory factor leukemia inhibitory factor receptor alpha Lif protein, mouse Lifr protein, mouse messenger RNA mitogen activated protein kinase 1 mitogen activated protein kinase 3 STAT3 protein Stat3 protein, mouse tyrosine unclassified drug animal cell animal experiment animal model article breast tumor cell survival female human human cell immunohistochemistry mouse nonhuman phosphorylation protein analysis protein expression protein function reverse transcription polymerase chain reaction Western blotting animal Bagg albino mouse cell culture experimental neoplasm fluorescent antibody technique genetics immunoprecipitation metabolism pathology signal transduction Animals Blotting, Western Cell Survival Female Fluorescent Antibody Technique Immunoprecipitation Leukemia Inhibitory Factor Leukemia Inhibitory Factor Receptor alpha Subunit Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Phosphorylation Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction STAT3 Transcription Factor Tumor Cells, Cultured Tyrosine
description	Introduction: It has been demonstrated that leukemia inhibitory factor (LIF) induces epithelium apoptosis through Stat3 activation during mouse mammary gland involution. In contrast, it has been shown that this transcription factor is commonly activated in breast cancer cells, although what causes this effect remains unknown. Here we have tested the hypothesis that locally produced LIF can be responsible for Stat3 activation in mouse mammary tumors. Methods: The studies were performed in different tumorigenic and non-tumorigenic mammary cells. The expression of LIF and LIF receptor was tested by RT-PCR analysis. In tumors, LIF and Stat3 proteins were analyzed by immunohistochemistry, whereas Stat3 and extracellular signal-regulated kinase (ERK)1/2 expression and phosphorylation were studied by Western blot analysis. A LIF-specific blocking antibody was used to determine whether this cytokine was responsible for Stat3 phosphorylation induced by conditioned medium. Specific pharmacological inhibitors (PD98059 and Stat3ip) that affect ERK1/2 and Stat3 activation were used to study their involvement in LIF-induced effects. To analyze cell survival, assays with crystal violet were performed. Results: High levels of LIF expression and activated Stat3 were found in mammary tumors growing in vivo and in their primary cultures. We found a single mouse mammary tumor cell line, LM3, that showed low levels of activated Stat3. Incidentally, these cells also showed very little expression of LIF receptor. This suggested that autocrine/paracrine LIF would be responsible for Stat3 activation in mouse mammary tumors. This hypothesis was confirmed by the ability of conditioned medium of mammary tumor primary cultures to induce Stat3 phosphorylation, activity that was prevented by pretreatment with LIF-blocking antibody. Besides, we found that LIF increased tumor cell viability. Interestingly, blocking Stat3 activation enhanced this effect in mammary tumor cells. Conclusion: LIF is overexpressed in mouse mammary tumors, where it acts as the main Stat3 activator. Interestingly, the positive LIF effect on tumor cell viability is not dependent on Stat3 activation, which inhibits tumor cell survival as it does in normal mammary epithelium. © 2007 Quaglino et al.; licensee BioMed Central Ltd.
format	Artículo Artículo publishedVersion
author	Quaglino, A. Schere-Levy, C. Romorini, L. Meiss, R.P. Kordon, E.C.
author_facet	Quaglino, A. Schere-Levy, C. Romorini, L. Meiss, R.P. Kordon, E.C.
author_sort	Quaglino, A.
title	Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling
title_short	Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling
title_full	Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling
title_fullStr	Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling
title_full_unstemmed	Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling
title_sort	mouse mammary tumors display stat3 activation dependent on leukemia inhibitory factor signaling
publishDate	2007
url	http://hdl.handle.net/20.500.12110/paper_14655411_v9_n5_p_Quaglino
work_keys_str_mv	AT quaglinoa mousemammarytumorsdisplaystat3activationdependentonleukemiainhibitoryfactorsignaling AT scherelevyc mousemammarytumorsdisplaystat3activationdependentonleukemiainhibitoryfactorsignaling AT romorinil mousemammarytumorsdisplaystat3activationdependentonleukemiainhibitoryfactorsignaling AT meissrp mousemammarytumorsdisplaystat3activationdependentonleukemiainhibitoryfactorsignaling AT kordonec mousemammarytumorsdisplaystat3activationdependentonleukemiainhibitoryfactorsignaling
_version_	1769810297505185792
spelling	paperaa:paper_14655411_v9_n5_p_Quaglino2023-06-12T16:50:21Z Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling Breast Cancer Res. 2007;9(5) Quaglino, A. Schere-Levy, C. Romorini, L. Meiss, R.P. Kordon, E.C. 2 (2 amino 3 methoxyphenyl)chromone crystal violet leukemia inhibitory factor mitogen activated protein kinase 1 mitogen activated protein kinase 3 protein antibody STAT3 protein leukemia inhibitory factor leukemia inhibitory factor receptor alpha Lif protein, mouse Lifr protein, mouse messenger RNA mitogen activated protein kinase 1 mitogen activated protein kinase 3 STAT3 protein Stat3 protein, mouse tyrosine unclassified drug animal cell animal experiment animal model article breast tumor cell survival female human human cell immunohistochemistry mouse nonhuman phosphorylation protein analysis protein expression protein function reverse transcription polymerase chain reaction Western blotting animal Bagg albino mouse cell culture experimental neoplasm fluorescent antibody technique genetics immunoprecipitation metabolism pathology signal transduction Animals Blotting, Western Cell Survival Female Fluorescent Antibody Technique Immunoprecipitation Leukemia Inhibitory Factor Leukemia Inhibitory Factor Receptor alpha Subunit Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Phosphorylation Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction STAT3 Transcription Factor Tumor Cells, Cultured Tyrosine Introduction: It has been demonstrated that leukemia inhibitory factor (LIF) induces epithelium apoptosis through Stat3 activation during mouse mammary gland involution. In contrast, it has been shown that this transcription factor is commonly activated in breast cancer cells, although what causes this effect remains unknown. Here we have tested the hypothesis that locally produced LIF can be responsible for Stat3 activation in mouse mammary tumors. Methods: The studies were performed in different tumorigenic and non-tumorigenic mammary cells. The expression of LIF and LIF receptor was tested by RT-PCR analysis. In tumors, LIF and Stat3 proteins were analyzed by immunohistochemistry, whereas Stat3 and extracellular signal-regulated kinase (ERK)1/2 expression and phosphorylation were studied by Western blot analysis. A LIF-specific blocking antibody was used to determine whether this cytokine was responsible for Stat3 phosphorylation induced by conditioned medium. Specific pharmacological inhibitors (PD98059 and Stat3ip) that affect ERK1/2 and Stat3 activation were used to study their involvement in LIF-induced effects. To analyze cell survival, assays with crystal violet were performed. Results: High levels of LIF expression and activated Stat3 were found in mammary tumors growing in vivo and in their primary cultures. We found a single mouse mammary tumor cell line, LM3, that showed low levels of activated Stat3. Incidentally, these cells also showed very little expression of LIF receptor. This suggested that autocrine/paracrine LIF would be responsible for Stat3 activation in mouse mammary tumors. This hypothesis was confirmed by the ability of conditioned medium of mammary tumor primary cultures to induce Stat3 phosphorylation, activity that was prevented by pretreatment with LIF-blocking antibody. Besides, we found that LIF increased tumor cell viability. Interestingly, blocking Stat3 activation enhanced this effect in mammary tumor cells. Conclusion: LIF is overexpressed in mouse mammary tumors, where it acts as the main Stat3 activator. Interestingly, the positive LIF effect on tumor cell viability is not dependent on Stat3 activation, which inhibits tumor cell survival as it does in normal mammary epithelium. © 2007 Quaglino et al.; licensee BioMed Central Ltd. Fil:Quaglino, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Schere-Levy, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Romorini, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kordon, E.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2007 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_14655411_v9_n5_p_Quaglino

Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling

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