Laminin Modulates the Stem Cell Population in LM05-E Murine Breast Cancer Cells Through the Activation of the MAPK/ERK Pathway

Autor: Damian E. Berardi, Laura B. Todaro, Marina Simian, Diego Raffo
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
MAPK/ERK pathway
Cancer Research
Stem cells
Mice
0302 clinical medicine
Laminin
Tumor Cells
Cultured
Cell Self Renewal
Tumor Stem Cell Assay
biology
Cell Differentiation
purl.org/becyt/ford/3.1 [https]
Cell biology
Medicina Básica
Oncology
030220 oncology & carcinogenesis
Neoplastic Stem Cells
Original Article
purl.org/becyt/ford/3 [https]
Stem cell
Signal transduction
medicine.drug
Homeobox protein NANOG
CIENCIAS MÉDICAS Y DE LA SALUD
MAP Kinase Signaling System
Inmunología
ESTROGEN RECEPTOR ALPHA
03 medical and health sciences
Cell Line
Tumor
medicine
Animals
Clonogenic assay
Protein kinase A
business.industry
Mammary Neoplasms
Experimental
LAMININ
Tamoxifen
030104 developmental biology
Drug Resistance
Neoplasm
Cancer research
biology.protein
Estrogen receptor alpha
Breast neoplasms
business
BREAST NEOPLASMS
Biomarkers
STEM CELLS
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Cancer Research and Treatment : Official Journal of Korean Cancer Association
Popis: PURPOSE: We investigated the effects of laminin on the fraction of cells with self-renewing capacity in the estrogen-dependent, tamoxifen-sensitive LM05-E breast cancer cell line. We also determined whether laminin affected the response to tamoxifen. MATERIALS AND METHODS: The LM05-E breast cancer cell line was used as a model for all experiments. Aldehyde dehydrogenase (ALDH) activity, clonogenic and mammosphere assays were performed to measure the effects of laminin on modulation of the stem cell subpopulation. Pluripotent gene expression was analyzed by RT-PCR. The involvement of the MAPK/ERK pathway was determined using specific inhibitors. The effects of laminin on the response to tamoxifen were determined and the involvement of alpha-6 integrin was investigated. RESULTS: We found that pre-treatment with laminin leads to a decrease in cells with the ability to form mammospheres that was accompanied by a decrease in ALDH activity. Moreover, exposure of mammospheres to laminin reduced the capacity to form secondary mammospheres and decreased the expression of Sox-2, Nanog and Oct-4. We previously reported that 4-OH-tamoxifen leads to an increase in the expression of these genes in LM05-E cells. Treatment with signaling pathway inhibitors revealed that the MAPK/ERK pathway mediates the effects of laminin. Finally, laminin induced tamoxifen resistance in LM05-E cells through alpha 6 integrin. CONCLUSIONS: Our results suggest that the final number of cells with self-renewing capacity in estrogen-dependent breast tumors may result from the combined effects of endocrine treatment and microenvironmental cues. Fil: Berardi, Damian Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Raffo, Diego Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Todaro, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Simian, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina
Databáze: OpenAIRE
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