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Nucleolar function and size in cancer cells.
- Source :
-
The American journal of pathology [Am J Pathol] 1998 May; Vol. 152 (5), pp. 1291-7. - Publication Year :
- 1998
-
Abstract
- We have have studied the relationship between nucleolar function and size and cell doubling time in cancer cells. Seven human cancer cell lines characterized by different proliferation rates were used. Nucleolar functional activity was evaluated by measuring RNA polymerase I activity and expression of RNA polymerase I upstream binding factor (UBF), DNA topoisomerase I, and fibrillarin, three proteins involved in synthesis and processing of rRNA. Transcriptional activity of RNA polymerase I was strictly related to cell doubling time (r = -0.97; P < 0.001). The quantitative distribution of UBF, DNA topoisomerase I, and fibrillarin was evaluated on Western blots using specific monoclonal antibodies by densitometric analysis of autoradiographic signals. It was found to be directly related to RNA polymerase I transcriptional activity (r = 0.89, P = 0.008 for UBF; r = 0.95, P = 0.001 for DNA topoisomerase I; and r = 0.91, P = 0.004 for fibrillarin) and inversely related to cell doubling time (r = -0.87, P = 0.011 for UBF; r = -0.97, P < 0.001 for DNA topoisomerase I; and r = -0.91, P = 0.005 for fibrillarin). The nucleolar areas were measured by automated image analysis on toluidine blue-stained cells. The values of the stained nucleolar structures per cell were directly related to RNA polymerase I transcriptional activity (r = 0.94, P = 0.001) and inversely related to cell doubling time (r = -0.98, P < 0.001). The same area values of the nucleolar structures stained by toluidine blue were also closely related to the amount of UBF (r = 0.92, P = 0.003), DNA topoisomerase I (r = 0.98, P < 0.001), and fibrillarin (r = 0.95, P = 0.001), and to the in situ quantitative distribution of AgNOR proteins (r = 0.98, P < 0.001). Our results demonstrated that in cancer cells rRNA transcriptional activity and nucleolar size are inversely related to cell doubling time. Quantitative distribution of nucleolar structures within the cell represents a cytohistological parameter of the rapidity of cell proliferation.
- Subjects :
- Blotting, Western
Cell Division
Cell Nucleolus genetics
Cell Nucleolus metabolism
Chromosomal Proteins, Non-Histone metabolism
DNA Topoisomerases, Type I metabolism
DNA, Neoplasm analysis
DNA-Binding Proteins metabolism
Electrophoresis, Polyacrylamide Gel
Female
Humans
Neoplasms genetics
Neoplasms metabolism
Nuclear Proteins metabolism
RNA Polymerase I metabolism
RNA, Neoplasm genetics
RNA, Neoplasm metabolism
RNA, Ribosomal metabolism
Transcription Factors metabolism
Cell Nucleolus pathology
Neoplasms pathology
Pol1 Transcription Initiation Complex Proteins
Tumor Cells, Cultured pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9440
- Volume :
- 152
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 9588897