BMC Seminar Thursday, 19th November at 12:00 Room 343 Læknagarður

Speaker: Bylgja Hilmarsdóttir, PhD Student at the Biomedical Center, University of Iceland.

Title: Inhibition of PTP1B in breast epithelial cells disrupts cell adhesion and induces anoikis

Abstract: Protein tyrosine phosphatase 1B (PTP1B) has been linked to breast cancer both as a tumor suppressor and as an oncogene. Currently there, is limiting information about the role of PTP1B in normal human breast epithelial cells. In this study, we analyzed the PTP1B expression in normal breast tissue where PTP1B is widely expressed in both epithelial and stromal cells.  D492 is breast epithelial stem cell line that form branching structures reminiscent of terminal duct lobular units (TDLU) when cultured in three-dimensional reconstituted basement membrane matrix (3D-rBM). PTP1B is widely expressed in these TDLU-like structures with higher expression associated with the lobular ends. Inhibition of PTP1B resulted in reduced proliferation and increased apoptosis in D492 cells. When looking at the phenotypic changes of D492 treated with PTP1B inhibitor, cells show anoikis-like effects, demonstrated by loose cell-cell adhesion and lack of the classical blebbing and shrinkage phenotype of apoptoic cells.  These changes were both seen when cells were cultured in monolayer and in 3D-rBM. These changes are associated with dramatic down-regulation of adhesion molecules such as occludin and claudin.  In conclusion, we have shown that PTP1B is widely expressed in the human breast gland with highest expression in myoepithelial cells. Inhibition of PTP1B in D492 breast epithelial stem cell line affects cell-cell adhesion and induces anoikis-like effects making PTP1B an important survival marker of breast epithelial cells in culture.