scholarly journals Transgenic overexpression of NanogP8 in the mouse prostate is insufficient to initiate tumorigenesis but weakly promotes tumor development in the Hi-Myc mouse model

Oncotarget ◽  
2017 ◽  
Vol 8 (32) ◽  
pp. 52746-52760
Author(s):  
Bigang Liu ◽  
Shuai Gong ◽  
Qiuhui Li ◽  
Xin Chen ◽  
John Moore ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tumor Development ◽  
Mouse Prostate

scholarly journals Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor development in a mouse model of ovarian cancer

2010 ◽  
Vol 107 (46) ◽  
pp. 19997-20002 ◽  
Author(s):  
F. Su ◽  
K. R. Kozak ◽  
S. Imaizumi ◽  
F. Gao ◽  
M. W. Amneus ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Tumor Development ◽  
Apolipoprotein A ◽  
Mimetic Peptides

Mouse model and human patient data suggest critical roles for Pten and p53 in suppressing POLE mutant tumor development

2021 ◽  
Author(s):  
Vivian S Park ◽  
Meijuan JS Sun ◽  
Wesley D Frey ◽  
Leonard G Williams ◽  
Karl P Hodel ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mouse Model ◽  
Genome Stability ◽  
Nuclear Dna ◽  
Tumor Development ◽  
Base Substitution ◽  
Human Patient ◽  
Mutation Burden ◽  
P53 Activation ◽  
Subsequent Loss

Mutations in the exonuclease domain of POLE are associated with tumors harboring very high mutation burdens. The mechanisms linking this significant mutation accumulation and tumor development remain poorly understood. Pole+/P286R;Trp53+/- mice showed accelerated cancer mortality compared to Pole+/P286R;Trp53+/+ mice. Cells from Pole+/P286R mice showed increased p53 activation, and subsequent loss of p53 permitted rapid growth, implicating canonical p53 loss of heterozygosity in POLE mutant tumor growth. Somewhat surprisingly, however, p53 status had no effect on tumor mutation burden or single base substitution signatures in POLE mutant tumors from mice or humans. Pten has important roles in maintaining genome stability. We find that PTEN mutations are highly enriched in human POLE mutant tumors, including many in POLE signature contexts. One such signature mutation, PTEN-F341V, was previously shown in a mouse model to specifically decrease nuclear Pten and lead to increased DNA damage. We found tumors in Pole+/P286R mice that spontaneously acquired PtenF341V mutations and were associated with significantly reduced nuclear Pten and elevated DNA damage. Taken together with recent published work, our results support the idea that POLE-mediated hypermutagenesis is necessary, but not entirely sufficient, for tumorigenesis. Disabling surveillance of nuclear DNA damage is a likely sufficient factor.

Carnitines slow down tumor development of colon cancer in the DMH-chemical carcinogenesis mouse model

2013 ◽  
Vol 114 (7) ◽  
pp. 1665-1673 ◽  
Author(s):  
Giuseppe Roscilli ◽  
Emanuele Marra ◽  
Federica Mori ◽  
Arianna Di Napoli ◽  
Rita Mancini ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mouse Model ◽  
Tumor Development ◽  
Chemical Carcinogenesis

scholarly journals Homozygous KSR1 deletion attenuates morbidity but does not prevent tumor development in a mouse model of RAS-driven pancreatic cancer

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0194998
Author(s):  
Elizabeth A. Germino ◽  
Joseph P. Miller ◽  
Lauri Diehl ◽  
Carter J. Swanson ◽  
Steffen Durinck ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Tumor Development

scholarly journals Knockdown of IKKβ Inhibits Tumor Development in a Leptomeningeal Metastasis Mouse Model and Proliferation of Lung Cancer Cells

2020 ◽  
Vol Volume 12 ◽  
pp. 6007-6017
Author(s):  
Yakun Liu ◽  
Yuanyuan Li ◽  
Zhongyao Li ◽  
Chunyan Li ◽  
Junying He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Tumor Development ◽  
Leptomeningeal Metastasis ◽  
Lung Cancer Cells

Role of GM-CSF in a mouse model of experimental autoimmune prostatitis

2019 ◽  
Vol 317 (1) ◽  
pp. F23-F29 ◽  
Author(s):  
Yaxiao Liu ◽  
Yan Li ◽  
Qinggang Liu ◽  
Zonglong Wu ◽  
Jianfeng Cui ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dorsal Root Ganglia ◽  
Knockout Mice ◽  
Dorsal Root ◽  
Prostate Tissue ◽  
Mrna Levels ◽  
Gm Csf ◽  
Mouse Prostate ◽  
Experimental Autoimmune

The etiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to play an important role in the development of autoimmune and inflammatory diseases. Here, we investigated the expression and function of GM-CSF in patients with CP/CPPS and in a mouse model of experimental autoimmune prostatitis (EAP). GM-CSF mRNA levels were detected in expressed prostatic secretions samples from patients with CP/CPPS and in prostate tissue from a mouse model of EAP. The expression of GM-CSF receptor in mouse prostate and dorsal root ganglia were determined using PCR and immunohistochemistry. Behavioral testing and inflammation scoring were performed to evaluate the role of GM-CSF in disease development and symptom severity of EAP using GM-CSF knockout mice. mRNA levels of putative nociceptive and inflammatory markers were measured in the prostate after the induction of EAP. Elevated GM-CSF mRNA levels were observed in expressed prostatic secretions samples from patients with CP/CPPS compared with healthy volunteers. GM-CSF mRNA was also significantly increased in prostate tissue of the EAP mice model. The expression of GM-CSF receptors was confirmed in mouse prostate and dorsal root ganglia. GM-CSF knockout mice showed fewer Infiltrating leukocytes and pain symptoms after the induction of EAP. Deletion of GM-CSF significantly diminished EAP-induced increases of chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 3, and nerve growth factor mRNA expression. The results indicated that GM-CSF plays a functional role in the pathogenesis of EAP. GM-CSF may function as a signaling mediator for both inflammation and pain transduction in CP/CPPS.

A new CRISPR mediated intestinal tumor mouse model targeting four canonical tumor suppressor genes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16064-e16064
Author(s):  
Hajime Kashima ◽  
Daniel Veronese-Paniagua ◽  
Anthony Fischer ◽  
Blair Madison ◽  
Deborah Rubin
Keyword(s):  
Tumor Suppressor ◽  
Mouse Model ◽  
Tumor Suppressor Genes ◽  
Rapid Development ◽  
Tumor Development ◽  
Intestinal Tumor ◽  
Intestinal Tumors ◽  
Suppressor Genes ◽  
Intestinal Tumorigenesis ◽  
Guide Rnas

e16064 Background: Mouse models of intestinal tumorigenesis have been developed and many of them involve mutations in the Apc gene. However, human intestinal tumors contain multiple additional sporadic mutations in tumor suppressor genes (TSGs). Our goal is to develop a novel mouse model of intestinal tumorigenesis that can recapitulate the natural history of mutations in diverse stages of tumor development. Methods: We used multiple guide RNAs to achieve random mutations in the canonical TSGs, Apc, Pten, Smad4, and Tp53. We generated transgenic (PPAS) mice that constitutively express the appropriate guide RNAs. Moreover, we achieved inducible Cas9 expression in icCas9N mice intestine using the Villin promoter to drive both a doxycycline-dependent activator and a doxycycline-inactivated repressor. We fed the doxycycline chow to PPAS:icCas9 double transgenic mice from the age of 6 to 8 weeks, and harvested intestine at 12 weeks. Results: We examined seven PPAS;icCas9 mice, and detected intestinal tumors in all the mice. Two mice had small intestinal tumor, three mice had colonic tumor, and two mice had tumors in both small and large intestine. The average number of tumors were 0.86, 1.57, 2.43 in small intestine, colon, and both respectively. We analyzed mutations in 11 tumors in 6 mice. The mutation patterns of Apc, Pten, Smad4 and Tp53 in tumors shared three distinct patterns. One was characterized by mutations in all four TSGs (n = 9). The second showed mutation in APC and Smad4 and Pten (n = 1). The third showed mutation only in Tp53 (n = 1). Normal intestine and colon in PPAS:icCas9 mice had no mutations. Conclusions: This model provides a powerful platform for modeling intestinal tumorigenesis driven by the canonical signaling pathway which are commonly dysregulated in colon cancer. This model provides a means for rapid development of intestinal tumors in mice, enabling an investigation of the relationship between novel candidate regulators of tumorigenesis and the canonical signaling pathways regulated by these four common TSGs. [Table: see text]

scholarly journals Deletion of cathepsin H perturbs angiogenic switching, vascularization and growth of tumors in a mouse model of pancreatic islet cell cancer

2010 ◽  
Vol 391 (8) ◽  
Author(s):  
Vasilena Gocheva ◽  
Xiaoping Chen ◽  
Christoph Peters ◽  
Thomas Reinheckel ◽  
Johanna A. Joyce
Keyword(s):  
Mouse Model ◽  
Pancreatic Islet ◽  
Human Cancer ◽  
Cell Cancer ◽  
Tumor Development ◽  
Proteolytic Processing ◽  
Limited Information ◽  
Pancreatic Islet Cell ◽  
Cysteine Cathepsins ◽  
Cathepsin H

Abstract Proteases can regulate many aspects of tumor development as their actions, which include degradation of the extracellular matrix, proteolytic processing of chemokines and activation of other enzymes, influence several key tumorigenic processes. Members of one protease class, the cysteine cathepsins, have received increasing recognition for their involvement in cancer development, and numerous clinical studies have reported correlations between elevated cathepsin levels and malignant progression. This is also the case for cathepsin H, a member of the cysteine cathepsin family, and its utility as a prognostic marker has been analyzed extensively. However, there is limited information available on its specific functions in tumor development and progression. To gain further insight into the role of this protease in cancer, we crossed cathepsin H-deficient mice with the RIP1-Tag2 model of pancreatic islet carcinogenesis. Deletion of cathepsin H significantly impaired angiogenic switching of the pre-malignant hyperplastic islets and resulted in a reduction in the subsequent number of tumors that formed. Moreover, the tumor burden in cathepsin H null RT2 mice was significantly reduced, in association with defects in the blood vasculature and increased apoptosis. Thus, we demonstrate here for the first time important tumor-promoting roles for cathepsin H in vivo using a mouse model of human cancer.

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