scholarly journals PTEN C-Terminal Deletion Causes Genomic Instability and Tumor Development

Cell Reports ◽  
2014 ◽  
Vol 6 (5) ◽  
pp. 844-854 ◽  
Author(s):  
Zhuo Sun ◽  
Chuanxin Huang ◽  
Jinxue He ◽  
Kristy L. Lamb ◽  
Xi Kang ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Tumor Development ◽  
Terminal Deletion

scholarly journals Control of Genomic Instability and Epithelial Tumor Development by the p53-Fbxw7/Cdc4 Pathway

2005 ◽  
Vol 65 (15) ◽  
pp. 6488-6492 ◽  
Author(s):  
Jesus Perez-Losada ◽  
Jian-Hua Mao ◽  
Allan Balmain
Keyword(s):  
Genomic Instability ◽  
Tumor Development ◽  
Epithelial Tumor

Loss of NKX6.3 During Gastric Carcinogenesis Enhances Genomic Instability and Promote Tumor Development

2020 ◽  
Author(s):  
JungHwan Yoon ◽  
Hassan Ashktorab ◽  
Duane T. Smoot ◽  
Suk Woo Nam ◽  
Won Sang Park
Keyword(s):  
Genomic Instability ◽  
Tumor Development ◽  
Gastric Carcinogenesis ◽  
Promote Tumor Development

Genomic Instability, as Measured by Microsatellite Alterations, Is Not Associated with Liver Tumor Development in the Genetically Susceptible B6C3F1 Mouse

1997 ◽  
Vol 143 (1) ◽  
pp. 167-172 ◽  
Author(s):  
Tony R. Fox ◽  
Patrick J. McMillen ◽  
Robert R. Maronpot ◽  
Thomas L. Goldsworthy
Keyword(s):  
Genomic Instability ◽  
Liver Tumor ◽  
Tumor Development ◽  
B6c3f1 Mouse

scholarly journals Depletion of NK6 Homeobox 3 (NKX6.3) causes gastric carcinogenesis through copy number alterations by inducing impairment of DNA replication and repair regulation

Oncogenesis ◽  
2021 ◽  
Vol 10 (12) ◽  
Author(s):  
Jung Hwan Yoon ◽  
Jung Woo Eun ◽  
Hassan Ashktorab ◽  
Duane T. Smoot ◽  
Jeong kyu Kim ◽  
...  
Keyword(s):  
Dna Replication ◽  
Epithelial Cells ◽  
Genomic Instability ◽  
Copy Number ◽  
Tumor Development ◽  
Genomic Stability ◽  
Gastric Epithelial Cells ◽  
Copy Number Alterations ◽  
Dna Replication And Repair ◽  
Underlying Causes

AbstractGenomic stability maintenance requires correct DNA replication, chromosome segregation, and DNA repair, while defects of these processes result in tumor development or cell death. Although abnormalities in DNA replication and repair regulation are proposed as underlying causes for genomic instability, the detailed mechanism remains unclear. Here, we investigated whether NKX6.3 plays a role in the maintenance of genomic stability in gastric epithelial cells. NKX6.3 functioned as a transcription factor for CDT1 and RPA1, and its depletion increased replication fork rate, and fork asymmetry. Notably, we showed that abnormal DNA replication by the depletion of NKX6.3 caused DNA damage and induced homologous recombination inhibition. Depletion of NKX6.3 also caused copy number alterations of various genes in the vast chromosomal region. Hence, our findings underscore NKX6.3 might be a crucial factor of DNA replication and repair regulation from genomic instability in gastric epithelial cells.

Genomic Stability: A Novel Function of NF-Kb in Lymphomas.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3240-3240
Author(s):  
Sampath Ramachandiran ◽  
Arsene Adone ◽  
Xiangxue Guo ◽  
Albert Liao ◽  
Uston Robert Sunay ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genomic Instability ◽  
Cell Lines ◽  
Nuclear Localization ◽  
Time Course ◽  
Tumor Development ◽  
Genomic Stability ◽  
Centrosome Duplication ◽  
Cyclin G

Abstract Abstract 3240 Poster Board III-177 Lymphomas are heterogeneous diseases comprising multiple clinical and biological subgroups. Several studies have shown that genomic instability and constitutive activation of the NF-kB pathway are key features for lymphoma development (Shen M,Hematologica 2007). However, it remains unclear whether changes in activation of the canonical and non-canonical NF-kB pathways (rel-A/p50 and rel-B/p52, respectively) reflect a response to genomic instability and therefore promotes lymphomagenesis. To answer this question, we first demonstrated in two lymphoma cell lines (Daudi and OCI-Ly3) that DNA damage induced by Doxorubicin (2 mcg/mL) resulted in nuclear localization of rel-A and Rel-B. Then, to determine the role of each NF-kB pathway in DNA repair and centrosome duplication we compared the number of cells positive for phospo-H2aX (pH2aX) and centrosomes numbers (measured by gamma-tubulin) in p105-siRNA (canonical) and P100-siRNA (non-canonical) with luciferase-siRNA (control) expressing cells. Our results showed that the expression of p105 and p100 siRNAs increase the number of pH2aX (+) cells compared to control. Subsequently, a time course measuring pH2aX (+) cells was performed after treating p105, P100 and luciferase siRNA OCI-ly3 expressing cell lines with Doxorubicin (2 mcg/mL). In cells expressing luciferase siRNA, pH2aX (+) cells peak (60%) at 60 minutes (min) and return to normal at 120 min, in p105 siRNA –cells pH2aX peak at 90 min (90% + cells) and then decrease similarly to luciferase siRNA cells. P100 siRNA cells demonstrate a continuous increased in pH2aX (+) cells up to 80%. In addition, p100 siRNA expression was associated with centrosome amplification (>2 centrosomes in 20-30% of the cells vs. < 8% in p105 or Luciferase siRNA expressing cells). Also, the expression of NF-kB siRNAs delayed doxorubicin-induced phosphorylation of p53 (serine 15 – target of ATM) and CHK2. To evaluate whether the genomic instability caused by both NF-kB siRNAs affects tumor development, we performed xenograft experiments. Our results demonstrated that NF-kB siRNAs not only slow down tumor initiation but prevented tumor development (p105 siRNA= 8 days delayed and 22% were tumor free and p100 siRNA= 13.5 days delayed and 55% were tumor free compared to luciferase siRNA). To investigate these findings in primary tissues we measured the number of phospo-H2aX (+) cells and the levels of rel-A and rel-B nuclear localization in 40 primary lymphoma tumor samples. Our results demonstrated that phospo-H2aX levels inversely correlated with rel-B nuclear localization (r=-0.58, p<0.0001). To identify possible explanations for these results, gene expression analysis was performed in cells expressing NF-kB siRNAs. Our results demonstrated that p105 siRNA regulated genes involved in DNA repair (PPP2R5C, ING5, SYF2, SYF2, XRCC6, etc) and p100 siRNA regulated genes involved in both DNA repair and centrosome duplication (GADD45 alpha, cyclin G, REDD1, PCBP4, etc) consistent with our results above. Quantitative PCR for some these genes during a doxorubicin-time course confirmed GADD45 alpha, cyclin G, PCBP4 and SFRS6 to be induced. We explored further the role of GADD45 alpha in lymphomas and found that knock down of this protein increase doxorubicin sensitivity by 50-fold. Overall this study demonstrated that activation of each NF-kB pathway is essential for maintaining genomic stability and therefore promoting tumor resistance to chemotherapy in lymphomas. In addition, we identified that GADD45 alpha is important target of the non-canonical NF-kB pathway for mediating genomic stability. These findings provide the rationale for designing novel agents aiming at targeting key genes involved in genomic stability. Disclosures No relevant conflicts of interest to declare.

scholarly journals The miR-205-5p/BRCA1/RAD17 Axis Promotes Genomic Instability in Head and Neck Squamous Cell Carcinomas

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1347 ◽  
Author(s):  
Fabio Valenti ◽  
Andrea Sacconi ◽  
Federica Ganci ◽  
Giuseppe Grasso ◽  
Sabrina Strano ◽  
...  
Keyword(s):  
Dna Repair ◽  
Head And Neck ◽  
Genomic Instability ◽  
Squamous Cell ◽  
Messenger Rna ◽  
Residual Disease ◽  
Tumor Development ◽  
Mrna Levels

Defective DNA damage response (DDR) is frequently associated with tumorigenesis. Abrogation of DDR leads to genomic instability, which is one of the most common characteristics of human cancers. TP53 mutations with gain-of-function activity are associated with tumors under high replicative stress, high genomic instability, and reduced patient survival. The BRCA1 and RAD17 genes encode two pivotal DNA repair proteins required for proper cell-cycle regulation and maintenance of genomic stability. We initially evaluated whether miR-205-5p, a microRNA (miRNA) highly expressed in head and neck squamous cell carcinoma (HNSCC), targeted BRCA1 and RAD17 expression. We found that, in vitro and in vivo, BRCA1 and RAD17 are targets of miR-205-5p in HNSCC, leading to inefficient DNA repair and increased chromosomal instability. Conversely, miR-205-5p downregulation increased BRCA1 and RAD17 messenger RNA (mRNA) levels, leading to a reduction in in vivo tumor growth. Interestingly, miR-205-5p expression was significantly anti-correlated with BRCA1 and RAD17 targets. Furthermore, we documented that miR-205-5p expression was higher in tumoral and peritumoral HNSCC tissues than non-tumoral tissues in patients exhibiting reduced local recurrence-free survival. Collectively, these findings unveil miR-205-5p’s notable role in determining genomic instability in HNSCC through its selective targeting of BRCA1 and RAD17 gene expression. High miR-205-5p levels in the peritumoral tissues might be relevant for the early detection of minimal residual disease and pre-cancer molecular alterations involved in tumor development.

Altered thymic epithelial cells may be decisive for Moloney virus-induced lymphoma development

1983 ◽  
Vol 41 ◽  
pp. 784-785
Author(s):  
U.I. Heine ◽  
G.R.F. Krueger ◽  
E. Munoz ◽  
A. Karpinski
Keyword(s):  
Epithelial Cells ◽  
Leukemia Virus ◽  
Light And Electron Microscopy ◽  
Tumor Development ◽  
Current Evidence ◽  
Thymic Epithelial Cells ◽  
Thymic Tissue ◽  
Newborn Mice ◽  
Moloney Leukemia Virus ◽  
Differentiation Block

Infection of newborn mice with Moloney leukemia virus (M-MuLV) causes a T-cell differentiation block in the thymic cortex accompanied by proliferation and accumulation of prethymic lymphoblasts in the thymus and subsequent spreading of these cells to generate systemic lymphoma. Current evidence shows that thymic reticular epithelial cells (REC) provide a microenvironment necessary for the maturation of prethymic lymphoblasts to mature T-lymphocytes by secretion of various thymic factors. A change in that environment due to infection of REC by virus could be decisive for the failure of lymphoblasts to mature and thus contribute to lymphoma development.We have studied the morphology and distribution of the major thymic cell populations at different stages of tumorigenesis in Balb/c mice infected when newborn with 0.2ml M-MuLV suspension, 6.8 log FFU/ml. Thymic tissue taken at 1-2 weekly intervals up to tumor development was processed for light and electron microscopy, using glutaraldehyde-OsO4fixation and Epon-Araldite embedding.

Stage-Dependent Expression of an Angiogenic Agent and Vascular Organization in Experimental Skin Tumor Development

2003 ◽  
Vol 31 (5) ◽  
pp. 539-548 ◽  
Author(s):  
Veera Näyhä ◽  
Jaakko Laitakari ◽  
Frej Stenbäck
Keyword(s):  
Tumor Development ◽  
Skin Tumor

Genomic instability and radiation mutagenesis

1996 ◽  
Vol 93 ◽  
pp. 157-164 ◽  
Author(s):  
JB Little ◽  
C Li ◽  
H Nagasawa ◽  
T Pfenning ◽  
H Vetrovs
Keyword(s):  
Genomic Instability

Identification of circulating microrna pattern alteration during the tumor development using C38/C57BL/6 mouse tumor model

2012 ◽  
Vol 50 (05) ◽  
Author(s):  
Z Nagy ◽  
B Barták ◽  
S Spisák ◽  
B Wichmann ◽  
A Kalmár ◽  
...  
Keyword(s):  
Tumor Development ◽  
Tumor Model ◽  
Circulating Microrna ◽  
Mouse Tumor ◽  
Mouse Tumor Model
Sign in / Sign up

Export Citation Format

Share Document