siRNA Knockdown of Ribosomal Protein Gene RPL19 Abrogates the Aggressive Phenotype of Human Prostate Cancer
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Date
2011-07-22ICR Author
Author
Bee, A
Brewer, D
Beesley, C
Dodson, A
Forootan, S
Dickinson, T
Gerard, P
Lane, B
Yao, S
Cooper, CS
Djamgoz, MBA
Gosden, CM
Ke, Y
Foster, CS
Type
Journal Article
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Show full item recordAbstract
We provide novel functional data that posttranscriptional silencing of gene RPL19 using RNAi not only abrogates the malignant phenotype of PC-3M prostate cancer cells but is selective with respect to transcription and translation of other genes. Reducing RPL19 transcription modulates a subset of genes, evidenced by gene expression array analysis and Western blotting, but does not compromise cell proliferation or apoptosis in-vitro. However, growth of xenografted tumors containing the knocked-down RPL19 in-vivo is significantly reduced. Analysis of the modulated genes reveals induction of the non-malignant phenotype principally to involve perturbation of networks of transcription factors and cellular adhesion genes. The data provide evidence that extra-ribosomal regulatory functions of RPL19, beyond protein synthesis, are critical regulators of cellular phenotype. Targeting key members of affected networks identified by gene expression analysis raises the possibility of therapeutically stabilizing a benign phenotype generated by modulating the expression of an individual gene and thereafter constraining a malignant phenotype while leaving non-malignant tissues unaffected.
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Research team
Cell Transformation
Language
eng
License start date
2011-07-22
Citation
PLOS ONE, 2011, 6
Publisher
PUBLIC LIBRARY SCIENCE