Centrosome amplification and the development of cancer

D’Assoro, Antonino B.; Lingle, Wilma L.; Salisbury, Jeffrey L.

doi:10.1038/sj.onc.1205772

Cited by 245 publications

(212 citation statements)

References 133 publications

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“…Centrosome amplification frequently occurs in almost all types of cancer, and it is considered to be the major factor contributing to CIN in cancer cells (D'Assoro et al, 2002;Kawamura et al, 2004;Fukasawa, 2005). Chromosome instability is clinically malignant and thought to be a worsening prognostic factor .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a number of studies have shown centrosome amplification to be a contributing factor to CIN in tumour cells (D'Assoro et al, 2002;Doxsey, 2002;Kawamura et al, 2004). Therefore, centrosome amplification is considered to be a hallmark for CIN.…”

Section: The Number Of Centrosomes In U251mg and D54mg Cellsmentioning

confidence: 99%

“…Therefore, CIN was thought to be a clinical malignant feature in almost all types of malignant tumours. A number of studies have shown that centrosome amplification contributes to CIN in tumour cells (D'Assoro et al, 2002;Doxsey, 2002;Kawamura et al, 2004). The centrosome is a major microtubule-organising centre in animal cells (Doxsey, 2001).…”

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confidence: 99%

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Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

et al. 2008

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Glioblastoma is characterised by invasive growth and a high degree of radioresistance. Survivin, a regulator of chromosome segregation, is highly expressed and known to induce radioresistance in human gliomas. In this study, we examined the effect of survivin suppression on radiosensitivity in malignant glioma cells, while focusing on centrosome aberration and chromosome instability (CIN). We suppressed survivin by small interfering RNA transfection, and examined the radiosensitivity using a clonogenic assay and a trypan blue exclusion assay in U251MG (p53 mutant) and D54MG (p53 wild type) cells. To assess the CIN status, we determined the number of centrosomes using an immunofluorescence analysis, and the centromeric copy number by fluorescence in situ hybridisation. As a result, the radiosensitisation differed regarding the p53 status as U251MG cells quickly developed extreme centrosome amplification ( ¼ CIN) and enhanced the radiosensitivity, while centrosome amplification and radiosensitivity increased more gradually in D54MG cells. TUNEL assay showed that survivin inhibition did not lead to apoptosis after irradiation. This cell death was accompanied by an increased degree of aneuploidy, suggesting mitotic cell death. Therefore, survivin inhibition may be an attractive therapeutic target to overcome the radioresistance while, in addition, proper attention to CIN (centrosome number) is considered important for improving radiosensitivity in human glioma.

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Section: Discussionmentioning

confidence: 99%

Section: The Number Of Centrosomes In U251mg and D54mg Cellsmentioning

confidence: 99%

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Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

et al. 2008

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“…Functional deregulation and centrosome amplification which leads to abnormal spindle formation and chromosomal instability is strongly associated with tumorigenesis (Fukasawa et al, 1996;D'Assoro et al, 2002). Studies have shown that BRCA1 localizes to the centrosome and binds to g-tubulin, a major component of centrosomes (Starita et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene

et al. 2007

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Metastasis-associated tumor antigen 1 (MTA1), a component of the nucleosome remodeling and deacetylating (NuRD) complex is routinely upregulated in several cancers. In the present study, we investigated the potential role of MTA1 in BRCA1 transcriptional repression and subsequent chromosomal instability. MTA1-NuRD complex was found to negatively regulate BRCA1 transcription by physically associating with an atypical estrogen-responsive element (ERE) on the BRCA1 promoter. Moreover, MTA1 and HDAC complex recruited to the ERE of BRCA1 promoter in an ER a-dependent manner. Accordingly, BRCA1 protein levels were enhanced by silencing of either MTA1 expression or by treatment with the specific histone deacetylase inhibitor trichostatin A. MTA1's strong repressive effects on BRCA1 expression was supported by our observation that cells stably overexpressing MTA1 showed centrosome amplification which has been long implicated as a phenotype for BRCA1 repression. Accordingly, overexpression of BRCA1 in cells stably over expressing MTA1 resulted in restoration of normal centrosome numbers. Together, these findings strongly implicate MTA1 in the transcriptional repression of BRCA1 leading to abnormal centrosome number and chromosomal instability.

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“…Centrosome amplification and aneuploidy are common events triggered by the loss of tumor suppressors or by overexpression of oncogenes. The accuracy of centrosome duplication is therefore essential for maintenance of genomic stability and centrosome duplication is coupled to the cell division cycle (D'Assoro et al, 2002;Doxsey et al, 2005;Fukasawa 2005;Sluder 2005;Nigg 2006; Tsou and Stearns, 2006).…”

Section: Introductionmentioning

confidence: 99%

Antizyme, a mediator of ubiquitin-independent proteasomal degradation and its inhibitor localize to centrosomes and modulate centriole amplification

et al. 2007

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The potential tumor suppressor antizyme and its endogenous inhibitor (antizyme inhibitor, AZI) have been implicated in the ubiquitin-independent proteasomal degradation of proteins involved in cell proliferation as well as in the regulation of polyamine levels. We show here that both antizyme and AZI concentrate at centrosomes and that antizyme preferentially associates with the maternal centriole. Interestingly, alterations in the levels of these proteins have opposing effects on centrosomes. Depletion of antizyme in various cell lines and primary cells leads to centrosome overduplication, whereas overexpression of antizyme reduces numerical centrosome abnormalities. Conversely, silencing of the antizyme inhibitor, AZI, results in a decrease of numerical centrosome abnormalities, whereas overexpression of AZI leads to centrosome overduplication. We further show that the numerical centrosome abnormalities are due to daughter centriole amplification. In summary, our results demonstrate that alterations in the antizyme/AZI balance cause numerical centrosomal defects and suggest a role for ubiquitin-independent proteasomal degradation in centrosome duplication.

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Centrosome amplification and the development of cancer

Cited by 245 publications

References 133 publications

Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene

Antizyme, a mediator of ubiquitin-independent proteasomal degradation and its inhibitor localize to centrosomes and modulate centriole amplification

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