Browsing Scholarly Projects 2014 by Subjects
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Effect of ErbB4 on Triple Negative Breast Cancer Cell Growth and MigrationMembers of the ErbB subfamily of receptor tyrosine kinases are critical regulators of normal mammary gland development, and alterations in their signaling have been associated with breast tumorigenesis. ErbB4 expression in breast carcinomas predicts improved patient survival and inversely correlates with tumor grade, metastasis and disease recurrence. When examined in the context of the breast cancer molecular subtypes, ErbB4 expression is rarely expressed in the triple-negative tumor subtype, which is associated with poor prognosis. Recently, our lab discovered a genomic context for the loss of ErbB4 expression in metastatic, refractory triple-negative breast cancer (TNBC) samples by next generation sequencing technology. The goal of this study was to examine the effects of ErbB4 overexpression on the growth and migration of TNBC cell lines. A GFP-containing construct was used to overexpress ErbB4 in the ErbB4-negative TNBC cell lines BT-20, BT-549 and MDA-MB-468. An empty vector construct was used as the control. Expression was confirmed by western blot and fluorescence microscopy to detect expression of ErbB4 or GFP respectively. Cell motility and growth was assessed with a transwell migration assay and a sulforhodamine B assay to measure cell density, respectively. Our data indicates that overexpression of ErbB4 resulted in no significant difference in the migration of BT-549 or MDA-MB-468 cells but resulted in a slight increase in the migration of BT-20 cells. ErbB4 had a growth inhibitory effect on BT-549 and BT-20 cells but showed no difference in the growth of MDA-MB-468 cells. This data suggests that multiple ErbB4-mediated mechanisms occur to alter the growth of TNBC cells. Although the translational significance of ErbB4 loss may be in its ability to predict outcome in patients with TNBC, more work is needed to elucidate the molecular mechanisms mediating its function.