scholarly journals Auto-catalysed progression of aneuploidy explains the Hayflick limit of cultured cells, carcinogen-induced tumours in mice, and the age distribution of human cancer

2000 ◽  
Vol 348 (3) ◽  
pp. 497-506 ◽  
Author(s):  
David RASNICK
Keyword(s):  
Cancer Cells ◽  
Time Course ◽  
Cultured Cells ◽  
Human Cancer ◽  
Age Distribution ◽  
Spontaneous Transformation ◽  
Cells In Culture ◽  
Hayflick Limit ◽  
Modelling Studies ◽  
Diploid Cells

Evidence continues to accumulate that aneuploidy, an imbalance in the number of chromosomes, is responsible for the characteristic phenotypes of cancer, including the abnormal cellular size and morphology of cancer cells, the appearance of tumour-associated antigens, as well as the high levels of membrane-bound and secreted proteins responsible for invasiveness and loss of contact inhibition. Aneuploidy has also been demonstrated to be the self-perpetuating source of the karyotypic instability of cancer cells. Here it is shown that the auto-catalysed progression of aneuploidy explains the kinetics of the finite lifetime of diploid cells in culture, the time course of the appearance of papillomas and carcinomas in benzo[a]pyrene-treated mice, and the age-dependence of human cancers. Modelling studies indicate that the ease of spontaneous transformation of mouse cells in culture may be due to a chaotic progression of aneuploidy. Conversely, the strong preference towards senescence and resistance to transformation of human cells in culture may be the result of a non-chaotic progression of aneuploidy. Finally, a method is proposed for quantifying the aneuploidogenic potencies of carcinogens.

scholarly journals Adenovirus E4orf4 Protein-Induced Death of p53-/- H1299 Human Cancer Cells Follows a G1 Arrest of both Tetraploid and Diploid Cells due to a Failure To Initiate DNA Synthesis

2013 ◽  
Vol 87 (24) ◽  
pp. 13168-13178 ◽  
Author(s):  
L. Cabon ◽  
N. Sriskandarajah ◽  
M. Z. Mui ◽  
J. G. Teodoro ◽  
P. Blanchette ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Cancer Cells ◽  
Human Cancer ◽  
G1 Arrest ◽  
Human Cancer Cells ◽  
Diploid Cells

scholarly journals Selective vulnerability of aneuploid human cancer cells to inhibition of the spindle assembly checkpoint

2020 ◽  
Author(s):  
Yael Cohen-Sharir ◽  
James M. McFarland ◽  
Mai Abdusamad ◽  
Carolyn Marquis ◽  
Helen Tang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cellular Response ◽  
Large Scale ◽  
Spindle Assembly Checkpoint ◽  
Human Cancer ◽  
Spindle Assembly ◽  
Selective Vulnerability ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Diploid Cells

AbstractSelective targeting of aneuploid cells is an attractive strategy for cancer treatment. Here, we mapped the aneuploidy landscapes of ~1,000 human cancer cell lines and classified them by their degree of aneuploidy. Next, we performed a comprehensive analysis of large-scale genetic and chemical perturbation screens, in order to compare the cellular vulnerabilities between near-diploid and highly-aneuploid cancer cells. We identified and validated an increased sensitivity of aneuploid cancer cells to genetic perturbation of core components of the spindle assembly checkpoint (SAC), which ensures the proper segregation of chromosomes during mitosis. Surprisingly, we also found highly-aneuploid cancer cells to be less sensitive to short-term exposures to multiple inhibitors of the SAC regulator TTK. To resolve this paradox and to uncover its mechanistic basis, we established isogenic systems of near-diploid cells and their aneuploid derivatives. Using both genetic and chemical inhibition of BUB1B, MAD2 and TTK, we found that the cellular response to SAC inhibition depended on the duration of the assay, as aneuploid cancer cells became increasingly more sensitive to SAC inhibition over time. The increased ability of aneuploid cells to slip from mitotic arrest and to keep dividing in the presence of SAC inhibition was coupled to aberrant spindle geometry and dynamics. This resulted in a higher prevalence of mitotic defects, such as multipolar spindles, micronuclei formation and failed cytokinesis. Therefore, although aneuploid cancer cells can overcome SAC inhibition more readily than diploid cells, the proliferation of the resultant aberrant cells is jeopardized. At the molecular level, analysis of spindle proteins identified a specific mitotic kinesin, KIF18A, whose levels were drastically reduced in aneuploid cancer cells. Aneuploid cancer cells were particularly vulnerable to KIF18A depletion, and KIF18A overexpression restored the sensitivity of aneuploid cancer cells to SAC inhibition. In summary, we identified an increased vulnerability of aneuploid cancer cells to SAC inhibition and explored its cellular and molecular underpinnings. Our results reveal a novel synthetic lethal interaction between aneuploidy and the SAC, which may have direct therapeutic relevance for the clinical application of SAC inhibitors.

Violation of the Patterns of Distribution of Hela Cells on the Substrate during Low-Frequency Pulsed Electromagnetic Radiation Effect (15 HZ)

10.12737/5890 ◽  
2014 ◽  
Vol 21 (3) ◽  
pp. 18-22
Author(s):  
Омельчук ◽  
N. Omelchuk ◽  
Бунин ◽  
K. Bunin ◽  
Симаков ◽  
...  
Keyword(s):  
Electromagnetic Radiation ◽  
Cancer Cells ◽  
Hela Cells ◽  
Human Cancer ◽  
Low Frequency ◽  
Malignant Cells ◽  
Pulsed Field ◽  
Cells In Culture ◽  
Cell Line Hela ◽  
Pulsed Electromagnetic

The experiment was carried out on the cell line HeLa, which is one of the most famous among researchers, biologists and physicians; it is widely used in laboratories to identify factors that inhibit the cancerous growth, as well as for testing and testing of various drugs. It is shown that after 60 minutes of exposure field electromagnetic with a frequency of 15 Hz. from impulse wave of the device "Kamena" in the culture of cancer cells occurs morphological structural adjustment. HeLa cells are compressed and reduced contact with the substrate and form becomes elongated and wedge-shaped. In addition, under the influence of pulsed field electromagnetic with a frequency of 15 Hz patterns (patterns), formed by HeLa cells resembling a "flower", dissolved, and cells randomly appears in the culture. HeLa cells, after exposure to the field of apparatus "Kameny, become different dimension that allows to speak about the development of anisocytosis, which indicates a decrease in the resistance of cancer cells in culture for them to adverse factors. During the same time period in the control (without effects of pulsed EMR) is observed only move in HeLa cells relatively dark marks due to horizontal migration. This compression cells and destruction of patterns that originally marked in culture, in the form of the "flower", didn’t observed. Revealed the effect of low-frequency field electromagnetic on the morphology of cancer cells and on the patterns of their distribution on the substrate may be important for therapy of malignant tumors. This experiment doesn’t yet allow by the authors to answer the question: how long the effect on human cancer cells can be maintained in culture and how safe the use of this pulsed field EMR to inhibit the activity of malignant cells. In these experiments, the authors observed an increase in cell proliferation in culture of malignant cells. All of this suggests that further research of revealed effect of low-intensity pulsed electromagnetic radiation on malignant cells in culture is necessary.

scholarly journals Zebrafish xenograft model of human lung cancer for studying the function of LINC00152 in cell proliferation and invasion

2020 ◽  
Author(s):  
Wenyi Shen ◽  
Juan Pu ◽  
Jing Sun ◽  
Bing Tan ◽  
Wei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cultured Cells ◽  
Human Cancer ◽  
Xenograft Model ◽  
Lung Cancer Cells ◽  
Proliferation And Invasion

Abstract Background: Numerous studies show that long non-coding RNAs take important roles in human cancer progression. Although zebrafish xenograft become a novel in vivo model for human cancer research recently, whether it can be used for studying the function of lncRNAs remains unknown.Methods: In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies by using zebrafish xenograft also confirmed these roles of LINC00152. In vivo confocal imaging was also used to evaluate the function of LINC00152 in cell proliferation and migration more accurately. Pharmacology experiments were further performed to study the potential tumor treatment of LINC00152 downregulation combined with EGFR inhibitor in cultured cells and zebrafish xenograft.Results: Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro . In zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells by two imaging methods at different magnification. Moreover, knocking-down LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and zebrafish xenograft model.Conclusion: Our study reveals the oncogenic roles and potential tumor treatment target of LINC00152 in lung cancer cells by zebrafish xenograft models, suggesting that this model could be used for the functional and application study of human lncRNA in tumor biology.* Wenyi Shen and Juan Pu contributed equally to this work.

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