20. Increased Polo-like kinase 1 (Plk1) expression promotes centrosome amplification, chromosomal instability, and tumor formation in a mouse model

2021 ◽  
Vol 252-253 ◽  
pp. S7
Author(s):  
Lilia Gheghiani ◽  
Lei Wang ◽  
Youwei Zhang ◽  
Xavier Moore ◽  
Jinglei Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Chromosomal Instability ◽  
Tumor Formation ◽  
Centrosome Amplification ◽  
Plk1 Expression

scholarly journals Clinical implication of centrosome amplification in plasma cell neoplasm

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3669-3675 ◽  
Author(s):  
Wee J. Chng ◽  
Greg J. Ahmann ◽  
Kim Henderson ◽  
Rafael Santana-Davila ◽  
Philip R. Greipp ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multivariate Regression ◽  
Monoclonal Gammopathy ◽  
Chromosomal Instability ◽  
Centrosome Amplification ◽  
Expression Data ◽  
Potential Mechanism ◽  
Plasma Cell Neoplasm ◽  
Cell Neoplasm ◽  
Undetermined Significance

The mechanisms underlying aneuploidy in multiple myeloma (MM) are unclear. Centrosome amplification has been implicated as the cause of chromosomal instability in a variety of tumors and is a potential mechanism causing aneuploidy in MM. Using immunofluorescent (IF) staining, centrosome amplification was detected in 67% of monoclonal gammopathies, including monoclonal gammopathy of undetermined significance (MGUS). We also investigated the gene expression of centrosome proteins. Overall, gene expression data correlated well with IF-detected centrosome amplification, allowing us to derive a gene expression-based centrosome index (CI) as a surrogate for centrosome amplification. Clinically, MM patients with high CI (> 4) are associated with poor prognostic genetic and clinical subtypes (chromosome 13 deletion, t(4; 14), t(14;16), and PCLI > 1%, P < .05) and are shown here to have short survival (11.1 months versus 39.1 months, P < .001). On multivariate regression, a high CI is an independent prognostic factor. Given that centrosome amplification is already observed in MGUS and probably integral to early chromosomal instability and myeloma genesis, and patients with more extensive centrosome amplification have shorter survival, the mechanisms leading to centrosome amplification should be investigated because these may offer new avenues for therapeutic intervention.

scholarly journals Virulence protein VirD5 ofAgrobacterium tumefaciensbinds to kinetochores in host cells via an interaction with Spt4

2017 ◽  
Vol 114 (38) ◽  
pp. 10238-10243 ◽  
Author(s):  
Xiaorong Zhang ◽  
G. Paul H. van Heusden ◽  
Paul J. J. Hooykaas
Keyword(s):  
Chromosome Segregation ◽  
High Frequency ◽  
Chromosomal Instability ◽  
Plant Cells ◽  
Tumor Formation ◽  
Host Cells ◽  
Infection Site ◽  
Virulence Proteins ◽  
Virulence Protein

The bacteriumAgrobacterium tumefacienscauses crown gall tumor formation in plants. During infection the bacteria translocate an oncogenic piece of DNA (transferred DNA, T-DNA) into plant cells at the infection site. A number of virulence proteins are cotransported into host cells concomitantly with the T-DNA to effectuate transformation. Using yeast as a model host, we find that one of these proteins, VirD5, localizes to the centromeres/kinetochores in the nucleus of the host cells by its interaction with the conserved protein Spt4. VirD5 promotes chromosomal instability as seen by the high-frequency loss of a minichromosome in yeast. By using both yeast and plant cells with a chromosome that was specifically marked by alacOrepeat, chromosome segregation errors and the appearance of aneuploid cells due to the presence of VirD5 could be visualized in vivo. Thus, VirD5 is a prokaryotic virulence protein that interferes with mitosis.

scholarly journals Taurine Attenuates Carcinogenicity in Ulcerative Colitis-Colorectal Cancer Mouse Model

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Guifeng Wang ◽  
Ning Ma ◽  
Feng He ◽  
Shosuke Kawanishi ◽  
Hatasu Kobayashi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Drinking Water ◽  
Mouse Model ◽  
Histopathological Examination ◽  
Tumor Formation ◽  
Water Model ◽  
Control Group ◽  
Ki 67

Taurine (2-aminoethane-sulfonic acid) is a type of amino acids and has numerous physiological and therapeutic functions, including anti-inflammation. However, there are few studies on the anticancer action of taurine. Our previous studies have demonstrated that taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells in vitro. In this study, we have investigated whether taurine has an anticancer effect, using azoxymethane (AOM)/sulfate sodium (DSS)- induced mouse model for colon carcinogenesis. All mice, except those in control group, received a single intraperitoneal injection of AOM and DSS in the drinking water for 7 days twice, with 1-week interval. After the first DSS treatment, mice were given distilled water (model group) or taurine in the drinking water (taurine group) ad libitum. No tumor was observed in the control group. Taurine significantly suppressed AOM+DSS-induced tumor formation. Histopathological examination revealed AOM/DSS treatment induced colon cancer in all mice (8/8, 100%), and taurine significantly inhibited the progression of colon cancer (4/9, 44.4%). Taurine significantly attenuated cell proliferation in cancer tissues detected by Ki-67 staining. Taurine significantly increased the levels of an apoptosis marker cleaved caspase-9 and tumor suppressor protein PTEN. This is the first study that demonstrated that taurine significantly reduced carcinogenicity in vivo using AOM/DSS-induced colon cancer mouse model.

scholarly journals Combination therapy with atorvastatin and celecoxib delays tumor formation in a Fanconi anemia mouse model

2018 ◽  
Vol 66 (1) ◽  
pp. e27460 ◽  
Author(s):  
Qing-shuo Zhang ◽  
Matthew Deater ◽  
Ngoc Phan ◽  
Andrea Marcogliese ◽  
Angela Major ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Mouse Model ◽  
Fanconi Anemia ◽  
Tumor Formation

Abstract 2029: Mcph1/Brit1 deficiency promotes genomic instability and tumor formation in a mouse model

2015 ◽  
Author(s):  
Yulong Liang ◽  
Hong Gao ◽  
Shiaw-Yih Lin ◽  
John A. Goss ◽  
Chunying Du ◽  
...  
Keyword(s):  
Mouse Model ◽  
Genomic Instability ◽  
Tumor Formation

scholarly journals SIRT1 Catalytic Activity Has Little Effect on Tumor Formation and Metastases in a Mouse Model of Breast Cancer

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e82106 ◽  
Author(s):  
Katherine V. Clark-Knowles ◽  
Danielle Dewar-Darch ◽  
Karen E. Jardine ◽  
Michael W. McBurney
Keyword(s):  
Breast Cancer ◽  
Catalytic Activity ◽  
Mouse Model ◽  
Tumor Formation

scholarly journals Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research

2016 ◽  
Vol 113 (42) ◽  
pp. 11859-11864 ◽  
Author(s):  
Paul W. Tetteh ◽  
Kai Kretzschmar ◽  
Harry Begthel ◽  
Maaike van den Born ◽  
Jeroen Korving ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Small Intestine ◽  
Epithelial Cells ◽  
Mouse Model ◽  
Human Colon ◽  
Suppressor Gene ◽  
Proximal Colon ◽  
Tumor Formation ◽  
Cell Of Origin ◽  
Human Colon Cancer

Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic anhydrase I (Car1) is a gene expressed uniquely in colonic epithelial cells. We generated a colon-specific inducible Car1CreER knock-in (KI) mouse with broad Cre activity in epithelial cells of the proximal colon and cecum. Deletion of the tumor suppressor gene Apc using the Car1CreER KI caused tumor formation in the cecum but did not yield adenomas in the proximal colon. Mutation of both Apc and Kras yielded microadenomas in both the cecum and the proximal colon, which progressed to macroadenomas with significant morbidity. Aggressive carcinomas with some invasion into lymph nodes developed upon combined induction of oncogenic mutations of Apc, Kras, p53, and Smad4. Importantly, no adenomas were observed in the small intestine. Additionally, we observed tumors from differentiated Car1-expressing cells with Apc/Kras mutations, suggesting that a top-down model of intestinal tumorigenesis can occur with multiple mutations. Our results establish the Car1CreER KI as a valuable mouse model to study colon-specific tumorigenesis and metastasis as well as cancer-cell-of-origin questions.

scholarly journals Hyperinsulinemia promotes metastasis to the lung in a mouse model of Her2-mediated breast cancer

2013 ◽  
Vol 20 (3) ◽  
pp. 391-401 ◽  
Author(s):  
Rosalyn D Ferguson ◽  
Emily J Gallagher ◽  
Dara Cohen ◽  
Aviva Tobin-Hess ◽  
Nyosha Alikhani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Lung Metastases ◽  
Breast Cancer Incidence ◽  
Mesenchymal Cells ◽  
Tumor Formation ◽  
Metastatic Progression ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Incidence And Mortality

The Her2 oncogene is expressed in ∼25% of human breast cancers and is associated with metastatic progression and poor outcome. Epidemiological studies report that breast cancer incidence and mortality rates are higher in women with type 2 diabetes. Here, we use a mouse model of Her2-mediated breast cancer on a background of hyperinsulinemia to determine how elevated circulating insulin levels affect Her2-mediated primary tumor growth and lung metastasis. Hyperinsulinemic (MKR+/+) mice were crossed with doxycycline-inducible Neu-NT (MTB/TAN) mice to produce the MTB/TAN/MKR+/+ mouse model. Both MTB/TAN and MTB/TAN/MKR+/+ mice were administered doxycycline in drinking water to induce Neu-NT mammary tumor formation. In tumor tissues removed at 2, 4, and 6 weeks of Neu-NT overexpression, we observed increased tumor mass and higher phosphorylation of the insulin receptor/IGF1 receptor, suggesting that activation of these receptors in conditions of hyperinsulinemia could contribute to the increased growth of mammary tumors. After 12 weeks on doxycycline, although no further increase in tumor weight was observed in MTB/TAN/MKR+/+ compared with MTB/TAN mice, the number of lung metastases was significantly higher in MTB/TAN/MKR+/+ mice compared with controls (MTB/TAN/MKR+/+ 16.41±4.18 vs MTB/TAN 5.36±2.72). In tumors at the 6-week time point, we observed an increase in vimentin, a cytoskeletal protein and marker of mesenchymal cells, associated with epithelial-to-mesenchymal transition and cancer-associated fibroblasts. We conclude that hyperinsulinemia in MTB/TAN/MKR+/+ mice resulted in larger primary tumors, with more mesenchymal cells and therefore more aggressive tumors with more numerous pulmonary metastases.

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