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Jena, N, Deng, M, Sicinska, E, Sicinski, P and Daley, GQ (2002) Critical role for cyclin D2 in BCR/ABL-induced proliferation of hematopoietic cells. Cancer Res. 62:535-41
Chronic myeloid leukemia is caused by the tyrosine kinase oncoprotein BCR/ABL. Using oligonucleotide arrays to assay mRNAs at different phases of the cell cycle in BCR/ABL-transformed cells, we found that cyclin D2 mRNA was constitutively expressed at high levels throughout the cell cycle, a pattern confirmed by immunoblotting of protein lysates. Bone marrow cells from cyclin D2-deficient strains of mice failed to proliferate in response to infection with a retrovirus carrying BCR/ABL and failed to generate transformed lymphoid cell lines in vitro. These results establish that BCR/ABL promotes cell cycle progression by altering expression of cyclin D2 and that cyclin D2 induction plays a critical role in proliferation of hematopoietic cells by BCR/ABL.
Animals; Bone Marrow Cells/cytology; Cell Division/physiology; Cell Line, Transformed; Cell Transformation, Neoplastic/genetics; Cyclin D2; Cyclins/biosynthesis; Cyclins/genetics; Cyclins/physiology; Fusion Proteins, bcr-abl/biosynthesis; Fusion Proteins, bcr-abl/genetics; Fusion Proteins, bcr-abl/physiology; Gene Expression Profiling; Gene Expression Regulation/drug effects; Gene Expression Regulation/physiology; Genes, abl; Hematopoietic Stem Cells/metabolism; Mice; Oligonucleotide Array Sequence Analysis; RNA, Messenger/biosynthesis; RNA, Messenger/genetics; Signal Transduction; Tetracycline/pharmacology; Transcriptional Activation
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