title: Different effects of ribosome biogenesis inhibition on cell proliferation in retinoblastoma protein- and p53-deficient and proficient human osteosarcoma cell lines.
abstract: OBJECTIVE
  To evaluate the effects of rRNA synthesis inhibition on cell cycle progression and cell population growth according to the RB and p53 status.
  
  
  METHODS
  RB- and p53-proficient U2OS cells and the RB- and p53-deficient SAOS-2 cells were used, rRNA transcription hindered by actinomycin D, and cell cycle analysed by flow cytometry.
  
  
  RESULTS
  One hour of actinomycin D treatment induced in U2OS cells a block at the cell cycle checkpoints G(1)-S and G(2)-M, which was removed only after rRNA synthesis was resumed. rRNA synthesis inhibition did not influence cell cycle progression in SAOS-2 cells. No effect on cell cycle progression after actinomycin D-induced rRNA inhibition was also found in U2OS cells silenced for RB and p53 expression. A mild perturbation of cell cycle progression was observed in U2OS cells silenced for the expression of either RB or p53 alone. We also treated U2OS and SAOS-2 cells with actinomycin D for 1 h/day for 5 days. This treatment lightly reduced growth rate of the U2OS cell population, whereas cell population growth of SAOS-2 cells was completely inhibited. A marked reduction of ribosome content occurred in SAOS-2 cells after the long-term actinomycin D treatment, whereas no modification was observed in U2OS cells.
  
  
  CONCLUSIONS
  These results demonstrate that inhibition of ribosome biogenesis does not hinder cell cycle progression in RB- and p53-deficient cells. A daily-repeated transitory inhibition of ribosome biogenesis leads to a progressive reduction of ribosome content with the consequent extinction of cancer cell population lacking RB and p53.
authors.affiliation: Dipartimento di Patologia Sperimentale, Università di Bologna, Bologna, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Montanaro
authors.forename: G
authors.initials: G
authors.lastname: Mazzini
authors.forename: S
authors.initials: S
authors.lastname: Barbieri
authors.forename: M
authors.initials: M
authors.lastname: Vici
authors.forename: A
authors.initials: A
authors.lastname: Nardi-Pantoli
authors.forename: M
authors.initials: M
authors.lastname: Govoni
authors.forename: G
authors.initials: G
authors.lastname: Donati
authors.forename: D
authors.initials: D
authors.lastname: Treré
authors.forename: M
authors.initials: M
authors.lastname: Derenzini
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019384:Nucleic Acid Synthesis Inhibitors; D012335:RNA, Ribosomal; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D003609:Dactinomycin