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dc.contributor.author
Daroqui, Maria Cecilia  
dc.contributor.author
Vazquez, Paula  
dc.contributor.author
Bal, Elisa Dora  
dc.contributor.author
Bakin, Andrei V.  
dc.contributor.author
Puricelli, Lydia I.  
dc.date.available
2017-02-10T19:29:03Z  
dc.date.issued
2012-08  
dc.identifier.citation
Daroqui, Maria Cecilia; Vazquez, Paula; Bal, Elisa Dora; Bakin, Andrei V.; Puricelli, Lydia I.; TGF-beta autocrine pathway and MAPK signaling promote cell invasiveness and in vivo mammary adenocarcinoma tumor progression; Spandidos Publ Ltd; Oncology Reports; 28; 2; 8-2012; 567-575  
dc.identifier.issn
1021-335X  
dc.identifier.uri
http://hdl.handle.net/11336/12865  
dc.description.abstract
Breast cancer progression and metastasis have been linked to abnormal signaling by transforming growth factor-beta (TGF-beta) cytokines. In early-stage breast cancers, TGF-beta exhibits tumor suppressor activity by repressing cell proliferation and inducing cell death, whereas in advanced-stage tumors, TGF-beta promotes invasion and metastatic dissemination. The molecular mechanisms underlying pro-oncogenic activities of TGF-beta are not fully understood. The present study validates the role of TGF-beta signaling in cancer progression and explores mediators of pro-oncogenic TGF-beta activities using the LM3 mammary adenocarcinoma cell line, derived from a spontaneous murine mammary adenocarcinoma. Expression of kinase-inactive TGF-beta receptors decreased both basal and TGF-beta-induced invasion. Analysis of signal transduction mediators showed that p38MAPK and MEK contribute to TGF-beta stimulation of cell motility and invasion. TGF-beta disrupted the epithelial actin structures supporting cell-cell adhesions, and increased linear actin filaments. Moreover, MEK and p38MAPK pathways showed opposite effects on actin remodeling in response to TGF-beta. Blockade of Raf-MEK signaling enhanced TGF-beta induction of actin stress-fibers whereas p38MAPK inhibitors blocked this effect. A novel observation was made that TGF-beta rapidly activates the actin nucleation Arp2/3 complex. In addition, TGF-beta stimulated matrix metalloproteinase MMP-9 secretion via a MAPK-independent pathway. Experiments using syngeneic mice showed that kinase-inactive TGF-beta receptors inhibit the first stages of LM3 tumor growth in vivo. Our studies demonstrate that autocrine TGF-beta signaling contributes to the invasive behavior of mammary carcinoma cells. Moreover, we show that both MAPK-dependent and -independent pathways are necessary for TGF-beta-induced effects. Therefore, MEK-ERK and p38 MAPK pathways are potential venues for therapeutic intervention in pro-oncogenic TGF-beta signaling.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Spandidos Publ Ltd  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Mammary Cancer Cell Line  
dc.subject
Tgf B  
dc.subject
Mapk Signaling Pathways  
dc.subject
Tumor Progression  
dc.subject.classification
Bioquímica y Biología Molecular  
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Medicina Básica  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
TGF-beta autocrine pathway and MAPK signaling promote cell invasiveness and in vivo mammary adenocarcinoma tumor progression  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2017-02-09T18:22:37Z  
dc.journal.volume
28  
dc.journal.number
2  
dc.journal.pagination
567-575  
dc.journal.pais
Grecia  
dc.journal.ciudad
Atenas  
dc.description.fil
Fil: Daroqui, Maria Cecilia. Montefiore Medical Center; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Vazquez, Paula. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina  
dc.description.fil
Fil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Bakin, Andrei V.. Roswell Park Cancer Institute; Estados Unidos  
dc.description.fil
Fil: Puricelli, Lydia I.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina  
dc.journal.title
Oncology Reports  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981025/  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.spandidos-publications.com/or/28/2/567