Aneuploidy, the somatic mutation that makes cancer a species of its own

Duesberg, Peter H.; Rasnick, David

doi:10.1002/1097-0169(200010)47:2<81::aid-cm1>3.0.co;2-#

Cited by 207 publications

(70 citation statements)

References 180 publications

(376 reference statements)

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“…This suggests that other genes on chromosome 7 are likely to be involved in mediating the observed biological effects, or that chromosome 7 aneusomy is serving as a marker for chromosomal instability, which confers an adverse prognosis in many tumors. 9,10 Another important point for discussion is the basis for the apparent synergistic effects that we observed of combining the prognostic factors. The observation that EGFR protein over-expression was not always linked to gene amplification suggests that EGFR over-expression is often mediated by other mechanisms.…”

Section: Discussionmentioning

confidence: 95%

Aberrant EGFR and Chromosome 7 Associate with Outcome in Laryngeal Cancer

Morrison¹,

Jacobson²,

Friedman

et al. 2005

The Laryngoscope

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Section: Discussionmentioning

confidence: 95%

Aberrant EGFR and Chromosome 7 Associate with Outcome in Laryngeal Cancer

Morrison¹,

Jacobson²,

Friedman

et al. 2005

The Laryngoscope

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“…They are therefore classified as typical Ames test-negative carcinogens [1]. Many of the chemicals considered to be carcinogenic are categorized as Ames test-negative [54]. Thus, how these carcinogens exert their effects and whether all Ames test-negative carcinogens produce aneuploidy through the Hog1-Swe1 pathway requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Phenyl hydroquinone, an Ames test‐negative carcinogen, induces Hog1‐dependent stress response signaling

Yamamoto¹,

Nunoshiba²,

Umezu³

et al. 2008

The FEBS Journal

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We have previously observed that phenyl hydroquinone (PHQ), a hepatic metabolite of the Ames testnegative carcinogen ortho-phenylphenol (OPP) [1,2], arrests the cell cycle at G 1 and G 2 ⁄ M and causes aneuploidy [3]. However, potential mechanisms for this activity have not yet been elucidated. Clarification of these mechanisms is important in understanding the mechanisms utilized by the Ames test-negative carcinogens OPP and PHQ, as well as the general mechanisms of aneuploidy development.A central principle of genetics is that cells within organisms contain the same complement of chromosomes. The presence of too many or too few chromosomes, called aneuploidy, is associated with diseases including cancer, and accounts for the majority of spontaneous miscarriages [4].A large number of genes that affect genome stability in budding yeast have been identified by mitotic defect mutation screens [5][6][7][8][9]. Many genes identified by other criteria have also been shown to be necessary for genome stability, including DNA metabolism enzymes such as polymerases, recombination enzymes and a ligase [10,11], as well as components of the chromosome segregation machinery, including tubulins, mitotic spindle Recently, we have shown that phenyl hydroquinone, a hepatic metabolite of the Ames test-negative carcinogen o-phenylphenol, efficiently induced aneuploidy in Saccharomyces cerevisiae. We further found that phenyl hydroquinone arrested the cell cycle at G 1 and G 2 ⁄ M. In this study, we demonstrate that phenyl hydroquinone can arrest the cell cycle at the G 2 ⁄ M transition as a result of stabilization of Swe1 (a Wee1 homolog), probably leading to inactivation of Cdc28 (a Cdk1 ⁄ Cdc2 homolog). Furthermore, Hog1 (a p38 MAPK homolog) was robustly phosphorylated by phenyl hydroquinone, which can stabilize Swe1. On the other hand, Chk1 and Rad53 were not phosphorylated by phenyl hydroquinone, indicating that the Mec1 ⁄ Tel1 DNA-damage checkpoint was not functional. Mutations of swe1 and hog1 abolished phenyl hydroquinone-induced arrest at the G 2 ⁄ M transition and the cells became resistant to phenyl hydroquinone lethality and aneuploidy development. These data suggest that a phenyl hydroqionone-induced G 2 ⁄ M transition checkpoint that is activated by the Hog1-Swe1 pathway plays a role in the development of aneuploidy.

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“…This interaction showed that ␥-syn association with BubR1 leads to a reduction in BubR1 protein by 26S proteasomal degradation but no decrease was observed in the mRNA levels (111). Thus, ␥-syn expression leads to over-riding the mitotic arrest allowing cells to continue progression through the cell cycle resulting in aneuploidy, a phenomenon that has been frequently observed in human cancer cell types (111,112). Furthermore, ␥-syn overexpression suppressed caspase 3 and caspase 9 activity disrupting the nocodazole-induced apoptotic response that would otherwise have resulted from normal BubR1 function (113).…”

Section: ␥-Syn In Cell Proliferationmentioning

confidence: 97%

γ‐Synuclein and the progression of cancer

Ahmad

Attoub²,

Singh

et al. 2007

FASEB j.

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The synucleins are a small, soluble, highly conserved group of neuronal proteins that have been implicated in both neurodegenerative diseases and cancer. The synuclein family consists of alpha-, beta-, and gamma-synucleins (gamma-syn). They are a natively unfolded group of proteins that share sequence homologies and structural properties. So far, the biological functions of the synucleins are still unclear, but their involvement in neurodegenerative diseases and cancer may provide insights into the pathological processes that result from these two groups of debilitating diseases, and present the possibility to use them as potential targets for early diagnosis and treatment. Recently, elevated levels of gamma-syn proteins have been detected in various types of cancer, especially in advanced stages of the disease. Furthermore, studies to date indicate that overexpression of gamma-syn compromises normal mitotic checkpoint controls, resulting in multinucleation as well as faster cell growth. Gamma-syn has also been shown to promote invasion and metastasis in in vitro assays as well as in animal models. Overexpression of gamma-syn also interferes with drug-induced apoptotic responses. These observations raise questions about the involvement of gamma-syn in the process of tumorigenesis and metastasis, and efforts have already been made to use gamma-syn as a marker for assessing breast cancer progression. This review will discuss the involvement of gamma-syn in cancer progression, metastasis and its potential as a marker.

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Aneuploidy, the somatic mutation that makes cancer a species of its own

Cited by 207 publications

References 180 publications

Aberrant EGFR and Chromosome 7 Associate with Outcome in Laryngeal Cancer

Aberrant EGFR and Chromosome 7 Associate with Outcome in Laryngeal Cancer

Phenyl hydroquinone, an Ames test‐negative carcinogen, induces Hog1‐dependent stress response signaling

γ‐Synuclein and the progression of cancer

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