Differential effect of phosphorylation-defective survivin on radiation response in estrogen receptor-positive and -negative breast cancer

PloS One
Bisrat G DebebWendy A Woodward

Abstract

Survivin is a key member of the inhibitor of apoptosis protein family, and is considered a promising therapeutic target due to its universal overexpression in cancers. Survivin is implicated in cellular radiation response through its role in apoptosis, cell division, and DNA damage response. In the present study, analysis of publically available data sets showed that survivin gene expression increased with breast cancer stage (p < 0.00001) and was significantly higher in estrogen receptor-negative cancers as compared to estrogen receptor-positive cancers (p = 9e-46). However, survivin was prognostic in estrogen receptor-positive tumors (p = 0.03) but not in estrogen receptor-negative tumors (p = 0.28). We assessed the effect of a survivin dominant-negative mutant on colony-formation (2D) and mammosphere-formation (3D) efficiency, and radiation response in the estrogen receptor-positive MCF7 and estrogen receptor-negative SUM149 breast cancer cell lines. The colony-formation efficiency was significantly lower in the dominant-negative survivin-transduced cells versus control MCF7 cells (0.42 vs. 0.58, p < 0.01), but it was significantly higher in dominant-negative population versus control-transduced SUM149 cells (0.29 vs. 0.20, ...Continue Reading

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Citations

Jun 4, 2016·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Dana-Adriana BotesteanuDoron Levy

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Methods Mentioned

BETA
antisense oligonucleotides
xenograft
immunoprecipitation

Software Mentioned

- Meier Plotter (
SigmaPlot
GraphPad
- M Plot )
FlowJo
Gene Expression - Based Outcome for Breast Cancer Online ( GOBO )
M Plot
Oncomine
Kaplan
Prism

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