Abstract
Cyclin D1, a key regulator of the cell cycle, acts as an oncogene when over-expressed in several types of cancer. In some B-chronic lymphoproliferative disorders, the over-expression of cyclin D1 protein is thought to confer a proliferative phenotype. We have generated BaF3 pro-B cell derivatives in which cyclin D1 can be induced rapidly and reversibly in a dose-dependent manner by the hormone muristerone A. When non-expressing clones displayed the same proliferative capacity as the parental cell line, in the sub-clones, a moderate induction of cyclin D1 lengthened the proliferation rate. The over-expression of cyclin D1 had the same effects on cell proliferation but also led ultimately to cell death by apoptosis. The induction of cyclin D1 in growth factor-deprived cells as well as in anticancer drug-treated cells also reinforced the magnitude of apoptosis. Thus, the expression of cyclin D1 in lymphoid cells does not confer a proliferative advantage but rather alters the response of cells towards apoptotic stimuli in a p53-independent manner.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apoptosis / drug effects*
-
B-Lymphocytes / cytology
-
B-Lymphocytes / metabolism*
-
Cell Cycle / drug effects
-
Cell Cycle Proteins / metabolism
-
Cell Division / drug effects
-
Cell Line
-
Cell Survival / drug effects
-
Clone Cells
-
Cyclin D1 / biosynthesis*
-
Cyclin D1 / genetics
-
Cyclin D1 / pharmacology
-
Cyclin-Dependent Kinase Inhibitor p21
-
Cyclins / metabolism
-
Dose-Response Relationship, Drug
-
Ecdysterone / analogs & derivatives*
-
Ecdysterone / pharmacology
-
Etoposide / pharmacology
-
Genetic Vectors / genetics
-
Genetic Vectors / metabolism
-
Interleukin-3 / pharmacology
-
Mice
-
Nucleic Acid Synthesis Inhibitors / pharmacology
-
Promoter Regions, Genetic / drug effects
-
Promoter Regions, Genetic / genetics
-
Proto-Oncogene Proteins / metabolism
-
Proto-Oncogene Proteins c-bcl-2*
-
Stem Cells / cytology
-
Stem Cells / metabolism*
-
Transfection
-
Tumor Suppressor Protein p53 / metabolism
-
bcl-2-Associated X Protein
Substances
-
Cdkn1a protein, mouse
-
Cell Cycle Proteins
-
Cyclin-Dependent Kinase Inhibitor p21
-
Cyclins
-
Interleukin-3
-
Nucleic Acid Synthesis Inhibitors
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-bcl-2
-
Tumor Suppressor Protein p53
-
bcl-2-Associated X Protein
-
Cyclin D1
-
muristerone A
-
Ecdysterone
-
Etoposide