1. Mechanical strain induces involution-associated events in mammary epithelial cells
- Author
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Ana Quaglino, Natalia Rubinstein, Edith C. Kordon, Jesica Vanesa Pellegrotti, and Marcelo Salierno
- Subjects
Mammary gland ,Gene Expression ,animal cell ,Leukemia Inhibitory Factor ,Mice ,0302 clinical medicine ,Bagg albino mouse ,cell stress ,Pregnancy ,Lif protein, mouse ,animal ,genetics ,Phosphorylation ,device ,Mitogen-Activated Protein Kinase 1 ,0303 health sciences ,Mice, Inbred BALB C ,Mitogen-Activated Protein Kinase 3 ,Stat3 protein, mouse ,lcsh:Cytology ,messenger RNA ,theoretical model ,weaning ,article ,equibiaxial stretching device ,cell line ,Cell biology ,medicine.anatomical_structure ,female ,udder ,030220 oncology & carcinogenesis ,microscopy ,Female ,Signal transduction ,breast epithelium ,Proto-Oncogene Proteins c-fos ,Research Article ,STAT3 Transcription Factor ,Cell type ,protein c fos ,animal experiment ,Biology ,artificial membrane ,Cell Line ,03 medical and health sciences ,Mammary Glands, Animal ,STAT3 protein ,image analysis ,medicine ,involution ,Animals ,controlled study ,RNA, Messenger ,lcsh:QH573-671 ,Mammary gland involution ,protein expression ,mouse ,030304 developmental biology ,cell culture ,nonhuman ,mechanical stress ,Epithelial Cells ,Cell Biology ,Epithelium ,protein phosphorylation ,mitogen activated protein kinase 3 ,mitogen activated protein kinase 1 ,Apoptosis ,Cell culture ,silicone ,cytology ,protein kinase B ,Stress, Mechanical ,epithelium cell ,Leukemia inhibitory factor ,metabolism - Abstract
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. Fil:Quaglino, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Salierno, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rubinstein, N. 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.
- Published
- 2009