Unscheduled expression of cyclin B1 and cyclin E in several leukemic and solid tumor cell lines.
Normal, nontumorous cells express cyclin proteins in an orderly, scheduled fashion, at a given phase of the cell cycle. Thus, cyclin B1 is synthesized during G2 and abruptly degraded during mitosis. The onset of cyclin E synthesis takes place in mid-G1, its maximal expression is at the time of cell entrance to S, and its degradation occurs during cell progression through S phase. In the present study, multiparameter flow cytometry was used to correlate expression of cyclin B1 or cyclin E with cell cycle position (estimated by cellular DNA content) in normal human proliferating lymphocytes as well as in T-cell MOLT-4 leukemia; promyelocytic HL-60 leukemia; histiocytic U937 lymphoma; MCF-7, T-47D, and Hs 587T breast carcinoma; Colo 320DM colon carcinoma; and the T-24 transitional cell carcinoma cell line. The scheduled expression of both cyclins, namely of cyclin B1 restricted to G2 + M cells and of cyclin E restricted to late G1 and early S cells, was observed only in normal lymphocytes and MOLT-4 cells. The cells of HL-60, U937, T-47D, and Hs 587T lines expressed both cyclins in an unscheduled ("ectopic") fashion, i.e., unrelated to cell cycle position. Colo 320DM cells showed unscheduled expression of cyclin E (i.e., during G2) but expression of cyclin B1 in this line was generally restricted to G2 + M cells. There were relatively few (10-12%) cells in MCF-7 and T-24 cell lines that expressed cyclin B1 or E in an unscheduled manner. It may be expected that the unscheduled expression of cyclins in tumor cells may lead to a loss of the regulatory mechanisms of cell cycle progression and that such feature of the tumor may be of prognostic value. There is a need, therefore, to conduct similar studies in primary tumor cells.
Gong
J
J
Cancer Research Institute, New York Medical College, Valhalla 10595.
Ardelt
B
B
Traganos
F
F
Darzynkiewicz
Z
Z
D002453:Cell Cycle / Q000502:physiology*; D016213:Cyclins / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D016193:G1 Phase / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D016213:Cyclins; D004273:DNA, Neoplasm