Establishment of an in vitro estrogen-dependent mouse mammary tumor model: A new tool to understand estrogen responsiveness and development of tamoxifen resistance in the context of stromal-epithelial interactions

Currently, to our knowledge, there are no continuous cell lines derived from estrogen dependent, tamoxifen sensitive spontaneous mouse mammary carcinomas. We describe here the establishment and characterization of a cell line derived from the M05 mouse mammary tumor, LM05-Mix, composed of both an ep...

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Detalles Bibliográficos
Autores: Pontiggia, Osvaldo Alejandro, Rodriguez, Vanina, Fabris, Victoria Teresa, Raffo, Diego Alejandro, Bumaschny, Viviana Florencia, Fiszman, Gabriel Leon, Bal, Elisa Dora, Simian, Marina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/151519
Acceso en línea:http://hdl.handle.net/11336/151519
Access Level:acceso abierto
Palabra clave:ESTROGEN DEPENDENT MOUSE MAMMARY CANCER
BICELLULAR CELL LINE
ESTROGEN AND PROGESTERONE RECEPTORS
TAMOXIFEN
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
Descripción
Sumario:Currently, to our knowledge, there are no continuous cell lines derived from estrogen dependent, tamoxifen sensitive spontaneous mouse mammary carcinomas. We describe here the establishment and characterization of a cell line derived from the M05 mouse mammary tumor, LM05-Mix, composed of both an epithelial and a fibroblastic component. From it the respective epithelial LM05-E and fibroblastic LM05-F cell lines were generated by limiting dilution. Immunofluorescence studies confirmed that the epithelial cells were positive for E-cadherin, cytokeratins and vimentin whereas the fibroblastic cells were negative for the epithelial markers and positive for a-smooth muscle actin and vimentin. Both cell types expressed estrogen and progesterone receptors, although only the epithelial LM05-E cells were stimulated by estradiol and inhibited by tamoxifen. In the bicellular LM05-Mix cell line estradiol proved to stimulate cell proliferation whereas the response to tamoxifen was dependent on confluency and the degree of epithelial-fibroblastic interactions. The presence of membrane estrogen receptors in both cell types was suggested by the achievement of non-genomic responses to short treatments with estradiol, leading to the phosphorylation of ERK1/2. Finally, cytogenetic studies suggest that these two cell types represent independent cell populations within the tumor and would not be the result of an epithelial-mesenchymal transition. This model presents itself as a valuable alternative for the study of estrogen responsiveness and tamoxifen resistance in the context of epithelial-stromal interactions.