Search results for "aneuploidy"

Aneuploidy induced by MAD2 haploinsufficiency triggers premature senescence in human primary fibroblast

2009

Early induction of genetic instability and apoptosis by arsenic in cultured Chinese hamster cells

2002

In order to assess at what time from the beginning of exposure inorganic arsenic can give rise to genetic instability and trigger apoptosis, V79-C13 Chinese hamster cells were treated with 10 microM sodium arsenite for 24 h. Under these conditions, cell survival was >70% and cells showed neither an increase in chromosome aberration frequency nor a delay in cell cycle progression. Investigations, which were carried out every 6 h during the treatment, revealed an early appearance of genetically unstable cells, namely micronucleated, multinucleated and mononucleated 'giant' cells, as well as apoptotic cells. Indirect immunostaining using anti-beta-tubulin antibody showed severe alterations in …

Pathogenic correlation between mosaic variegated aneuploidy 1 (MVA1) and a novel BUB1B variant: a reappraisal of a severe syndrome.

2022

Funder: Università degli Studi di Catania

Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts

2021

The centromere is a fundamental chromosome structure in which the macro-molecular kinetochore assembles and is bound by spindle microtubules, allowing the segregation of sister chromatids during mitosis. Any alterations in kinetochore assembly or functioning or kinetochore–microtubule attachments jeopardize chromosome stability, leading to aneuploidy, a common feature of cancer cells. The spindle assembly checkpoint (SAC) supervises this process, ensuring a faithful segregation of chromosomes. CENP-E is both a protein of the kinetochore and a crucial component of the SAC required for kinetochore–microtubule capture and stable attachment, as well as congression of chromosomes to the metaphas…

MYCN gain and MYCN amplification in a stage 4S neuroblastoma.

2003

Abstract Stage 4S neuroblastoma is a disease associated with spontaneous regression and good survival. We present a patient whose evolution has shown the variety and complexity of this disease in infants. Biologic factors, such as ploidy, MYCN copy number, loss of 1p36, and other chromosomal gains and losses were determined. A complex pattern of genetic abnormalities, such as near-diploidy, MYCN gain (2–4 copies per haploid genome) and imbalance/deletion of 1p36 was seen in the diagnostic sample. An extensive disseminated disease after a latent period of 26 months was associated with a special genetic evolution, such as tetraploidy, MYCN amplification (2:100–500 copies), 1p36 deletion, and …

Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian cells

2004

Early genetic instability induced in dividing V79-Cl3 Chinese hamster cells by inorganic arsenic, as demonstrated in our previous investigation, was evidenced by aneuploidy and nuclear abnormalities, but not by chromosomal rearrangements. Here we report the results of cytogenetic and morphological analyses performed on the progeny of cells dividing at the end of sodium arsenite treatment after they had been expanded through 120 generations (ASO cells) and then cloned. The acquired genetic instability persisted and was increased by highly unstable chromosomal rearrangements, namely dicentric chromosomes and telomeric associations, which were not seen following acute exposure. A peculiar find…

Centrosome amplification induced by hydroxyurea leads to aneuploidy in pRB deficient human and mouse fibroblasts.

2006

Alterations in the number and/or morphology of centrosomes are frequently observed in human tumours. However, it is still debated if a direct link between supernumerary centrosomes and tumorigenesis exists and if centrosome amplification could directly cause aneuploidy. Here, we report that hydroxyurea treatment induced centrosome amplification in both human fibroblasts expressing the HPV16 -E6-E7 oncoproteins, which act principally by targeting p53 and pRB, respectively, and in conditional pRB deficient mouse fibroblasts. Following hydroxyurea removal both normal and p53 deficient human fibroblasts arrested. On the contrary pRB deficient fibroblasts entered the cell cycle generating aneupl…

Interclonal heterogeneity in a human epithelioid-sarcoma cell line (Gru-1)

1994

Three clonal sub-populations, GRU-IA, GRU-IB, and GRU-IC, isolated from the human epithelioid sarcoma cell line GRU-I, were characterized morphologically, cytogenetically and with regard to proliferation kinetics. Immunocytochemically, major differences became evident in the expression of cytokeratin 18 and neurofilament proteins, which are indicative for epithelial and neural differentiation respectively. Vimentin, a mesenchymal differentiation marker, however, could be detected in all tumor cells of each sub-population. Laminin, a major compound of basement membranes, formed abundant intercellular network-like patterns in GRU-IB and GRU-IC, whereas GRU-IA was characterized by a diffuse in…

Aurora-A Transcriptional Silencing and Vincristine Treatment Show a Synergistic Effect in Human Tumor Cells

2008

Aurora-A is a centrosome-associated serine/threonine kinase that is overexpressed in multiple types of human tumors. Primarily, Aurora-A functions in centrosome maturation and mitotic spindle assembly. Overexpression of Aurora-A induces centrosome amplification and G 2 /M cell cycle progression. Recently, it was observed that overexpression of Aurora-A renders cells resistant to cisplatin (CDDP)-, etoposide-, and paclitaxel-induced apoptosis.Our results indicate that already in initial stages of cancer progression Aurora-A overexpression could have a major role in inducing supernumerary centrosomes and aneuploidy, as shown by immunohistochemistry on tissue sections from various stages of hu…

RB acute loss induces centrosome amplification and aneuploidy in murine primary fibroblasts

2006

AbstractBackgroundIncorrect segregation of whole chromosomes or parts of chromosome leads to aneuploidy commonly observed in cancer. The correct centrosome duplication, assuring assembly of a bipolar mitotic spindle, is essential for chromosome segregation fidelity and preventing aneuploidy. Alteration of p53 and pRb functions by expression of HPV16-E6 and E7 oncoproteins has been associated with centrosome amplification. However, these last findings could be the result of targeting cellular proteins in addition to pRb by HPV16-E7 oncoprotein. To get a more detailed picture on the role of pRb in chromosomal instability and centrosome amplification, we analyzed the effects of the acute loss …