Málstofa Lífvísindaseturs verður haldin fimmtudaginn 10. apríl kl. 12:25-13:10 í stofu 343 í Læknagarði.
Bylgja Hilmarsdóttir doktorsnemi við Læknadeild Háskóla Íslands mun flytja erindið: miR-200c-141 yfirtjáning snýr við bandvefsumbreytingu brjóstastofnfrumna og stýrir þeim í átt að kirtilþekjufrumusvipgerð
Leiðbeinendur Bylgju eru Þórarinn Guðjónsson og Magnús Karl Magnússon prófessorar við Læknadeild HÍ.
Erindið verður flutt á ensku og er öllum opið
This week BMC seminar will be given by Bylgja Hilmarsdóttir PhD student.
Title: Epithelial to mesenchymal transition in breast epithelial stem cells is reversed toward luminal epithelial differentiation by overexpression of miRNA-200c-141
Thursday 10 April at 12:25 in room 343 at Læknagarður
Abstract: The breast gland is composed of two epithelial lineages, the luminal- and myoepithelial derived from a common stem cell population. D492 is a breast epithelial cell line with stem cell properties that generates luminal- and myoepithelial cells in monolayer and form elaborate branching structures in 3D culture. We have recently shown in organotypic 3D culture that endothelial cells create a cellular niche for branching morphogenesis and epithelial to mesenchymal transition (EMT) of D492 cells. The EMT phenotype is evidenced by formation of spindle-like cells, suppression of keratins and a switch from E- to N-cadherin. In this study we have mapped the changes in microRNAs (miRNAs) expression in D492 compared to its mesenchymal-derivative D492M. Suppression of the miRNA-200 family in D492M was among the most profound changes. Bisulfite sequencing showed that the promoter region of miR-200c-141 was methylated in D492M but not in D492. Overexpression of miR-200c-141 in D492M (D492MmiR-200c-141) reversed the EMT phenotype resulting in loss of N-cadherin and Snail expression and gain of E-cadherin and EpCAM expression. Interestingly, D492MmiR-200c-141 failed to rescue expression of myoepithelial markers such as p63, P-cadherin, cytokeratin 5/6, 14 and 17. In contrast, introduction of p63 into D492M (D492Mp63) rescued only the myoepithelial phenotype. When cultured in matrigel D492MmiR-200c-141 cells form incomplete branching structures and were resistant to endothelial-induced EMT. Overexpression of p63 in D492MmiR-200c-141 resulted in complete reversion of protein expression in 2D culture to the D492 phenotype, where the cells express both luminal- and myopthelial markers. Moreover D492MmiR-200c-141-p63 form branching structures in 3D culture. In conclusion, our data suggests that p63 and miR-200c-141 are key regulators of breast epithelial differentiation towards luminal and myoepithelial differentiation.