Mechanical strain induces involution-associated events in mammary epithelial cells

Background: Shortly after weaning, a complex multi-step process that leads to massive epithelial apoptosis is triggered by tissue local factors in the mouse mammary gland. Several reports have demonstrated the relevance of mechanical stress to induce adaptive responses in different cell types. Inter...

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Detalles Bibliográficos
Autores: Quaglino, A., Salierno, M., Pellegrotti, J., Rubinstein, N., Kordon, E.C.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:Argentina
Institución:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
Repositorio:Biblioteca Digital (UBA-FCEN)
Idioma:inglés
OAI Identifier:paperaa:paper_14712121_v10_n_p_Quaglino
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_14712121_v10_n_p_Quaglino
Access Level:acceso abierto
Palabra clave:leukemia inhibitory factor
messenger RNA
mitogen activated protein kinase 1
protein c fos
protein kinase B
silicone
STAT3 protein
Lif protein, mouse
mitogen activated protein kinase 3
Stat3 protein, mouse
animal cell
animal experiment
article
artificial membrane
Bagg albino mouse
breast epithelium
cell culture
cell stress
controlled study
device
epithelium cell
equibiaxial stretching device
female
image analysis
involution
mechanical stress
microscopy
mouse
nonhuman
protein expression
protein phosphorylation
theoretical model
weaning
animal
cell line
cytology
gene expression
genetics
metabolism
phosphorylation
pregnancy
udder
Animals
Cell Line
Epithelial Cells
Female
Gene Expression
Leukemia Inhibitory Factor
Mammary Glands, Animal
Mice
Mice, Inbred BALB C
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Phosphorylation
Pregnancy
Proto-Oncogene Proteins c-fos
RNA, Messenger
STAT3 Transcription Factor
Stress, Mechanical
Descripción
Sumario:Background: Shortly after weaning, a complex multi-step process that leads to massive epithelial apoptosis is triggered by tissue local factors in the mouse mammary gland. Several reports have demonstrated the relevance of mechanical stress to induce adaptive responses in different cell types. Interestingly, these signaling pathways also participate in mammary gland involution. Then, it has been suggested that cell stretching caused by milk accumulation after weaning might be the first stimulus that initiates the complete remodeling of the mammary gland. However, no previous report has demonstrated the impact of mechanical stress on mammary cell physiology. To address this issue, we have designed a new practical device that allowed us to evaluate the effects of radial stretching on mammary epithelial cells in culture. Results: We have designed and built a new device to analyze the biological consequences of applying mechanical stress to cells cultured on flexible silicone membranes. Subsequently, a geometrical model that predicted the percentage of radial strain applied to the elastic substrate was developed. By microscopic image analysis, the adjustment of these calculations to the actual strain exerted on the attached cells was verified. The studies described herein were all performed in the HC11 non-tumorigenic mammary epithelial cell line, which was originated from a pregnant BALB/c mouse. In these cells, as previously observed in other tissue types, mechanical stress induced ERK1/2 phosphorylation and c-Fos mRNA and protein expression. In addition, we found that mammary cell stretching triggered involution associated cellular events as Leukemia Inhibitory Factor (LIF) expression induction, STAT3 activation and AKT phosphorylation inhibition. Conclusion: Here, we show for the first time, that mechanical strain is able to induce weaning-associated events in cultured mammary epithelial cells. These results were obtained using a new practical and affordable device specifically designed for such a purpose. We believe that our results indicate the relevance of mechanical stress among the early post-lactation events that lead to mammary gland involution. © 2009 Quaglino et al., licensee BioMed Central Ltd.