Bladder Cancer: Basic Research IModerated Poster 24774 DIFFERENTIAL EXPRESSION OF NOTCH-1 AND NOTCH-2 CORRELATES TO INVASIVE PHENOTYPE IN BLADDER CANCER CELL LINES
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INTRODUCTION AND OBJECTIVES
The Notch pathway plays a critical role in growth and differentiation, and is involved in cancer progression in different organ sites. Little is known about Notch in bladder cancer. In this study, we evaluated Notch-1 and Notch-2 expression in a panel of bladder cancer cell lines.
METHODS
Thirteen bladder cancer cell lines with previously described invasive properties and epithelial/mesenchymal characteristics were screened for Notch-1 and Notch-2 expression by Western blot and real-time PCR. Immunohistochemistry (IHC) was performed on a tissue microarray (US Biomax, Inc., Rockville, MD) that included cores from 152 patients with bladder cancer. Alterations in gene expression after Notch-2 silencing with siRNA were measured by expression microarray in 3 cell lines. Genes that
RESULTS
Epithelial cell lines with low invasive potential expressed Notch-1 at high and Notch-2 at low relative levels (p = 0.03 and p<0.01, respectively, compared to invasive cell lines). Highly invasive, mesenchymal cell lines expressed high levels of Notch-2 and low levels of Notch-1. These results were validated by Western blot and IHC (TMA). Microarray analysis revealed altered expression of genes related to epithelial to mesenchymal transition (EMT), protein and endosome trafficking, and
CONCLUSIONS
These results provide preliminary evidence for a role for Notch in the progression of bladder cancer and it is suggested that this may be related to EMT. Further investigation is needed to assess the suitability of Notch as a therapeutic target, and it would appear that selective inhibition of individual Notch receptors may be preferential over global inhibition.
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Source of Funding: Canadian Urologic Association Scholarship
Vancouver Coastal Health “in it for life” Award