Histology and histopathology Vol.15, nº 2 (2000)

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Browsing Histology and histopathology Vol.15, nº 2 (2000) by Subject "Cell cycle"

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    Gain of function properties of mutant p53 proteins at the mitotic spindle cell cycle checkpoint
    (Murcia : F. Hernández, 2000) Hixon, M.L.; Flores, A.; Wagner, M.; Gualberto, A.
    Mutations in the p53 tumor suppressor gene locus predispose human cells to chromosomal instability. This is due in part to interference of mutant p53 proteins with the activity of the mitotic spindle and postmitotic cell cycle checkpoints. Recent data demonstrates that wild type p53 is required for postmitotic checkpoint activity, but plays no role at the mitotic spindle checkpoint. Likewise, structural dominant p53 mutants demonstrate gain-of-function properties at the mitotic spindle checkpoint and dominant negative properties at the postmitotic checkpoint. At mitosis, mutant p53 proteins interfere with the control of the metaphase-toanaphase progression by up-regulating the expression of CKsl, a protein that mediates activatory phosphorylation of the anaphase promoting complex (APC) by Cdc2. Cells that carry mutant p53 proteins overexpress CKsl and are unable to sustain APC inactivation and mitotic arrest. Thus, mutant p53 gain-of-function at mitosis constitutes a key component to the origin of chromosomal instability in mutant p53 cells.
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    Vascular smooth muscle cell proliferation in the pathogenesis of atherosclerotic cardiovascular diseases
    (Murcia : F. Hernández, 2000) Rivard, A.; Andres, V.
    Atherosclerosis is the principal cause of myocardial infarction, stroke, and peripheral vascular disease, accounting for nearly half of all mortality in developed countries. For example, it has been estimated that atherosclerosis leads to approximately 500,000 deaths from coronary artery disease and 150,000 deaths from stroke every year in the United States (American Heart Association, 1996). Percutaneous transluminal angioplasty has become a well-established technique for revascularization of occluded arteries. However, the long-term efficacy of the procedure remains limited by progressive vessel renarrowing (restenosis) within the following few months after angioplasty. Abnormal vascular smooth muscle cell (VSMC) proliferation is thought to play an important role in the pathogenesis of both atherosclerosis and restenosis. Accordingly, considerable effort has been devoted to elucidate the mechanisms that regulate cell cycle progression in VSMCs. In the present article, we will review the different factors that are involved in the control of VSMC proliferation, especially in the context of cardiovascular disease. Ultimately, a thorough understanding of these regulatory networks may lead to the development of novel drug and gene therapies for the treatment of cardiovascular diseases. Therapeutic approaches that targeted specific cell-cycle control genes or growth regulatory molecules which effectively inhibited neointimal lesion formation will be also discussed.