Different effects of ribosome biogenesis inhibition on cell proliferation in retinoblastoma protein- and p53-deficient and proficient human osteosarcoma cell lines.

Abstract

OBJECTIVES:

To evaluate the effects of rRNA synthesis inhibition on cell cycle progression and cell population growth according to the RB and p53 status.

MATERIAL AND 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: L Montanaro, G Mazzini, S Barbieri, M Vici, A Nardi-Pantoli, M Govoni, G Donati, D Treré, M Derenzini
• Journal: Cell proliferation (Cell Prolif) Vol. 40 Issue 4 Pg. 532-49 (Aug 2007) ISSN: 0960-7722 [Print] England
• PMID: 17635520 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Nucleic Acid Synthesis Inhibitors
• RNA, Ribosomal
• Retinoblastoma Protein
• Tumor Suppressor Protein p53
• Dactinomycin

Topics

• Bone Neoplasms (metabolism, pathology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Dactinomycin (pharmacology)
• Humans
• Nucleic Acid Synthesis Inhibitors (pharmacology)
• Osteosarcoma (metabolism, pathology)
• RNA Interference
• RNA, Ribosomal (biosynthesis)
• Retinoblastoma Protein (antagonists & inhibitors, metabolism)
• Ribosomes (metabolism)
• Tumor Suppressor Protein p53 (antagonists & inhibitors, metabolism)