Chromosomal instability and cytoskeletal defects in oral cancer cells.

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 01/2000; 97(1):303-8.
Source: PubMed

ABSTRACT Oral squamous cell carcinomas are characterized by complex, often near-triploid karyotypes with structural and numerical variations superimposed on the initial clonal chromosomal alterations. We used immunohistochemistry combined with classical cytogenetic analysis and spectral karyotyping to investigate the chromosomal segregation defects in cultured oral squamous cell carcinoma cells. During division, these cells frequently exhibit lagging chromosomes at both metaphase and anaphase, suggesting defects in the mitotic apparatus or kinetochore. Dicentric anaphase chromatin bridges and structurally altered chromosomes with consistent long arms and variable short arms, as well as the presence of gene amplification, suggested the occurrence of breakage-fusion-bridge cycles. Some anaphase bridges were observed to persist into telophase, resulting in chromosomal exclusion from the reforming nucleus and micronucleus formation. Multipolar spindles were found to various degrees in the oral squamous cell carcinoma lines. In the multipolar spindles, the poles demonstrated different levels of chromosomal capture and alignment, indicating functional differences between the poles. Some spindle poles showed premature splitting of centrosomal material, a precursor to full separation of the microtubule organizing centers. These results indicate that some of the chromosomal instability observed within these cancer cells might be the result of cytoskeletal defects and breakage-fusion-bridge cycles.

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Available from: Susanne M Gollin, Feb 21, 2014
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    • "Acytokinetic tripolar mitosis has been proposed as a physiological mechanism of formation of trinucleate trophoblast giant cells in the bovine placenta (Klisch et al., 1999). Pathological occurrences include most cancers (Lingle et al., 2002; Ghadimi et al., 2000; Saunders et al., 2000), preneoplastic lesions (Chan, 2011), and various sick and infected cells (Mrak et al., 1995). Experimentally and therapeutically, tripolar mitosis can be induced by mitotic spindle toxins, some of them such as Paclitaxel or Vinblastine are used in chemotherapy (Demidenko et al., 2008; Speicher et al., 1992; reviewed by Chan et al., 2012), as well as by radiation doses such as those used in the treatment of tumors (Dodson et al., 2007). "
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    Acta Histochemica 12/2014; 100(1). DOI:10.1016/j.acthis.2014.11.009 · 1.76 Impact Factor
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    Genome Research 07/2011; 22(2):232-45. DOI:10.1101/gr.117226.110 · 13.85 Impact Factor
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    • "Inmosttumoursexhibitingchromosomalinstability,BFBeventsandcentrosomal abnormalitiesoccurtogether(Saundersetal.2000;Gisselssonetal.,unpublished data).Inanalogy,mostmalignanttumoursexhibitbothstructuralandnumerical "
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    02/2011; DOI:10.4267/2042/37826
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