Document Detail

Key role of the achievement of an appropriate ribosomal RNA complement for G1-S phase transition in H4-II-E-C3 rat hepatoma cells.
MedLine Citation:
PMID:  15389582     Owner:  NLM     Status:  MEDLINE    
Cell growth is closely related to cell proliferation and an adequate ribosome biogenesis appears to be necessary for cell duplication. In the present study, we have investigated the relationship between rRNA synthesis and cell cycle progression. For this purpose, in a first set of experiments, we evaluated the effect of rRNA synthesis variation on cycle duration in asynchronously growing H4-II-E-C3 rat hepatoma cells. Cells were either treated with insulin or insulin plus actinomycin D (AMD). The hormone stimulated ribosome biogenesis, which was later followed by an increased synthesis of DNA and a shortening of cell doubling time (DT). Bivariate flow cytometry indicated that the reduced length of the cell cycle was mainly due to the shorter G1-phase. AMD, at the concentration of 0.04 microg/ml, hindered ribosome biogenesis without affecting heterogeneous RNA production. A 12-h reduction in ribosome biogenesis level by AMD caused a lowering of DNA synthesis and a lengthening of cell DT with a longer G1-phase. In a second set of experiments, we analyzed the cell content variations of 28S and 18S rRNA transcripts during G1 phase in H4-II-E-C3 cells, synchronized by serum deprivation, and then stimulated by serum, serum plus insulin, and serum plus insulin and AMD. In control cells, a progressive increase in rRNA content occurred until the highest value of rRNA content was reached 21 h after serum stimulation. In insulin-treated cells, the highest rRNA value was reached at 12 h whereas in AMD-treated cells, the rRNA quantity was constantly low until 18 h and then sharply increased at 21 h. In the three experimental conditions, the highest values of rRNA amount were reached at the end of G1 phase and were quite similar to one another. We also evaluated, by real-time RT-PCR, cyclin E mRNA expression, which appeared to sharply increase at those times in which the maximum increase in the rRNA content was observed. Our results indicated that the achievement of an appropriate amount of rRNA allows G1/S phase transition, probably by modulating the expression of cyclin E mRNA.
Massimo Derenzini; Lorenzo Montanaro; Alessandra Chillà; Elena Tosti; Manuela Vici; Stefania Barbieri; Marzia Govoni; Giuliano Mazzini; Davide Treré
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  202     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2004-11-30     Completed Date:  2005-02-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  483-91     Citation Subset:  IM    
Copyright Information:
2004 Wiley-Liss, Inc.
Dipartimento di Patologia Sperimentale, Sezione di Patologia Clinica, Università di Bologna, Bologna, Italia.
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MeSH Terms
Carcinoma, Hepatocellular / genetics*,  pathology*
Cell Division / drug effects
Cell Line, Tumor
Cyclin E / genetics
Dactinomycin / pharmacology
G1 Phase*
Insulin / pharmacology
Liver Neoplasms / genetics*,  pathology*
Nucleic Acid Synthesis Inhibitors / pharmacology
RNA, Messenger / metabolism
RNA, Ribosomal / metabolism*
S Phase*
Time Factors
Reg. No./Substance:
0/Cyclin E; 0/Nucleic Acid Synthesis Inhibitors; 0/RNA, Messenger; 0/RNA, Ribosomal; 11061-68-0/Insulin; 50-76-0/Dactinomycin

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