title: In vitro investigations of interphase and metaphase argyrophilic nucleolar organizer regions and cellular proliferation in the human urothelial cancer cell line HOK-1.
abstract: Detailed investigation of cell growth and nucleolar organizer region associated argyrophilic proteins (Ag-NORs) is necessary to assess a possible impact of Ag-NOR quantification on the diagnosis and prognosis of tumours. In this study, cellular proliferation of the transitional-cell carcinoma cell line HOK-1 was modulated over a period of 11 days by starvation and subsequent medium addition. Proliferation was determined daily by DNA flow cytometric estimation of S-phase fraction (SPF) and mitotic index (MI) calculation. The number and area of interphase Ag-NORs were quantified by automated image analysis daily and the number of Ag-NOR bearing chromosomes in metaphase was counted. In interphase nuclei, Ag-NOR area showed a highly significant correlation with SPF (p < 0.0001) whereas interphase Ag-NOR number showed significant correlation with MI (p < 0.05). A positive relationship between the number of Ag-NOR bearing chromosomes in metaphases and cellular proliferation was also observed. There is variability in Ag-NOR quantity during interphase and metaphase depending on growth conditions in vitro. Correlations of the number of interphase Ag-NORs with the MI on one hand and Ag-NOR area with SPF on the other provide further evidence that distribution and quantity of Ag-NORs are strongly influenced by the cell cycle phase within the structural-functional unit of the nucleolus.
authors.affiliation: Department of Pathology, University of Innsburck, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Hittmair
authors.forename: D
authors.initials: D
authors.lastname: Ofner
authors.forename: F
authors.initials: F
authors.lastname: Offner
authors.forename: H
authors.initials: H
authors.lastname: Feichtinger
authors.forename: C
authors.initials: C
authors.lastname: Ensinger
authors.forename: H
authors.initials: H
authors.lastname: Rogatsch
authors.forename: G
authors.initials: G
authors.lastname: Mikuz
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000473:pathology; D002455:Cell Division; D003470:Culture Media; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007399:Interphase; D008677:Metaphase; D008940:Mitotic Index; D009697:Nucleolus Organizer Region / Q000648:ultrastructure*; D016622:Silver Staining; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000648:ultrastructure*
chemical_list: D003470:Culture Media; D004273:DNA, Neoplasm