title: Abnormal expression pattern of cyclin E in tumour cells.
abstract: The expression pattern of cyclin E during the cell cycle was studied in normal and tumour cells in culture and in tumour biopsies. This pattern was found to be abnormal in tumour cells. A triple immunostaining protocol, digital microscopy and image analysis were used to find the position of the individual cells in the cell cycle and to measure the nuclear cyclin E levels. In normal cells, the number of cyclin E-positive cells decreased rapidly when the cells entered the S-phase. In the tumour cell lines, cyclin E was not downregulated in early S-phase, as in normal cells. Instead the number of cyclin E-positive cells remained high throughout S-phase, and the cyclin E staining intensity per cell often increased during S-phase. In about half of the analysed tumour cell lines, many cells stained positive for cyclin E even in the G(2)-phase. This abnormal expression over the cell cycle of cyclin E was also found in tumour biopsies from cervical, breast and prostatic carcinomas, even though it varied greatly between individual tumours. In some tumours, the expression pattern of cyclin E was similar to that of normal cells in culture, whereas in others high cyclin E levels could be seen in S-phase cells, as in the transformed cell lines. A high percentage of cells expressing cyclin E during S- or G(2)-phase was found to be related to poor outcome (p < 0.025) in a small group of cervical carcinoma patients (n = 12).
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Erlandsson
authors.forename: Carolina
authors.initials: C
authors.lastname: Wählby
authors.forename: Susanna
authors.initials: S
authors.lastname: Ekholm-Reed
authors.forename: Ann-Cathrin
authors.initials: AC
authors.lastname: Hellström
authors.forename: Ewert
authors.initials: E
authors.lastname: Bengtsson
authors.forename: Anders
authors.initials: A
authors.lastname: Zetterberg
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001973:Bromodeoxyuridine; D002453:Cell Cycle; D002461:Cell Line, Transformed; D019925:Cyclin A / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism*; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D019925:Cyclin A; D019927:Cyclin E; D001973:Bromodeoxyuridine