title: siRNA knockdown of ribosomal protein gene RPL19 abrogates the aggressive phenotype of human prostate cancer.
abstract: 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.
authors.affiliation: Section of Cellular Pathology and Molecular Genetics, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Alix
authors.initials: A
authors.lastname: Bee
authors.forename: Daniel
authors.initials: D
authors.lastname: Brewer
authors.forename: Carol
authors.initials: C
authors.lastname: Beesley
authors.forename: Andrew
authors.initials: A
authors.lastname: Dodson
authors.forename: Shiva
authors.initials: S
authors.lastname: Forootan
authors.forename: Timothy
authors.initials: T
authors.lastname: Dickinson
authors.forename: Patricia
authors.initials: P
authors.lastname: Gerard
authors.forename: Brian
authors.initials: B
authors.lastname: Lane
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.forename: Colin S
authors.initials: CS
authors.lastname: Cooper
authors.forename: Mustafa B A
authors.initials: MB
authors.lastname: Djamgoz
authors.forename: Christine M
authors.initials: CM
authors.lastname: Gosden
authors.forename: Youqiang
authors.initials: Y
authors.lastname: Ke
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Foster
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D012269:Ribosomal Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; C489092:RPL19 protein, human; D012269:Ribosomal Proteins