Critical role for cyclin D2 in BCR/ABL-induced proliferation of hematopoietic cells.
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.
Jena
Nilamani
N
Whitehead Institute, Cambridge, Massachusetts 02142, USA.
Deng
Ming
M
Sicinska
Eva
E
Sicinski
Piotr
P
Daley
George Q
GQ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016313:Genes, abl; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013752:Tetracycline / Q000494:pharmacology; D015533:Transcriptional Activation
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl; D013752:Tetracycline