The molecular basis of carcinogenesis: understanding the cell cycle clock.
The cell cycle clock is the central controller of cell proliferation that governs the progress of the cell through its growth cycle, its exit from the active cycle, and its decision to differentiate. Components of the clock are found to be functioning in an aberrant fashion in many types of malignancies. Notable among these is the retinoblastoma protein, pRB, which acts to restrain proliferation in normal cells and suffers inactivation in many types of tumour cells. Its activity is controlled by D-type cyclins in various cell types. We have deleted one of these cyclins--cyclin D1--from the mouse germline and find that its absence leads to a limited range of defects including hypoplastic retinae and the inability of the mammary epithelium to respond to pregnancy-associated hormonal stimulation. Cyclin D1 is overexpressed in many human breast cancers, pointing to a highly specific association of this cell cycle clock component with mammary cell proliferation.
Weinberg
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Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, USA.
D000204:Activity Cycles; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000502:physiology*; D016161:Genes, Retinoblastoma; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology*; D016160:Retinoblastoma Protein / Q000096:biosynthesis
D016213:Cyclins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases