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Showing 1 to 20 of 36 for “"mutant p53"”.
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Targeting mutant p53 in cSCCs
… patients with multiple cSCCs.<br/><br/>Wild-type p53 (wt-p53) has been shown to prevent cSCC development and induce tanning and sunburn responses in skin cells. However, TP53 mutations are found in over half of all human cancers and cSCC is no exception as TP53 mutational frequency in cSCCs is …
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An investigation of mutant p53 function.
The TP53 tumour suppressor gene is mutated in approximately 50% of all human cancers. The majority of these mutations are missense mutations resulting in the expression of a mutated form of the full-length p53 protein. This mutant protein exhibits a loss of tumour suppressive activity, …
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Functionality of mutant p53 in early tumorigenesis
TP53, encoding a stress-activated transcription factor, is commonly mutated in human cancers. Most of these mutations are missense mutations which, in the presence of WT-p53 (p53mut/+), can cause loss of function (LOF), dominant-negative (DN) and/or gain of function (GOF) activities. However, …
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MUTANT P53 AS A THERAPEUTIC TARGET IN CANCER
Identifying therapeutic approaches to target TP53 mutations has the potential to revolutionize cancer treatment. TP53, the gene that encodes the prominent tumor suppressor protein p53, is mutated and inactivated in half of sporadic human tumors. Additionally, individuals who harbor germline TP53 …
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The germline- and tissue-specific effects of endogenous point-mutant p53
p53 is frequently altered in human tumors through missense mutations that result in accumulation of mutant p53 protein. These mutations may confer dominant-negative or gain-of- function properties to p53. To ascertain the physiological effects of tumor-associated point- mutations in p53, the …
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MUTANT P53 REGULATION OF CXC-CHEMOKINE EXPRESSION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA
… sites of the body. It has been found that both mutant p53 and epidermal growth factor receptor (EGFR) signaling pathways function to increase the expression of CXCL5, which has been identified as a key mediator in the process of tumor metastasis. Previous data from our lab suggested that the p53 …
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Influence of genotoxic drug-induced post-translational modifications on mutant p53 stability and oncogenic activities
The tumour suppressor p53 is often disrupted by missense mutations that can result in p53 protein accumulation and acquisition of novel oncogenic activities. Various studies have demonstrated that DNA-damaging drugs currently used in the clinic aimed at activating wild type p53, can also stabilise …
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Study of the Gain-of-Function Mutant p53 and PARP1 in Triple-Negative Breast Cancer
<p>Cancer cells often lose expression of the p53 protein or express mutant forms of p53. Some of these mutant p53 proteins, called gain-of-function mutant p53, have gained oncogenic functions. Previously, our group observed mutant p53 R273H interacts with replicating DNA and upregulates the …
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Gain-of-Function Effects of Mutant p53 Explored Using a Three-Dimensional Culture Model of Breast Cancer
p53 is the most frequent target for mutation in human tumors and mutation at this locus is a common and early event in breast carcinogenesis. Breast tumors with mutated p53 often contain abundant levels of this mutant protein, which has been postulated to actively contribute to tumorigenesis by …
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The Effects of Gain of Function Mutant p53 and p63 on EPS8 and CXCL5 Expression in Head and Neck Squamous Cell Carcinoma
… a survival rate of less than 50%. A class of mutant p53, known as gain of function (GOF) mutant p53, has been found to be expressed in tumors in these patients. GOF mutant p53 not only loses the wild type tumor suppressor functions, but also gains aberrant functions that have been linked to …
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Contribution of the DNA binding domain of p53 to regulation of its stability
Tumour suppressor p53 is frequently mutated in cancers. While wild type p53 is normally a rapidly degraded protein, mutant forms of p53 are stabilised and accumulate to high levels in tumour cells. Several studies have shown that mutant p53 acquires oncogenic properties and actively contributes to …
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P53 mediated cell motility in H1299 lung cancer cells
<p>Studies have shown that gain-of- function mutant p53, AKT, and NFκB promote invasion and metastasis in tumor cells. Signals transduced by AKT and p53 are integrated via negative feedback between the two pathways. Tumor derived p53 was also indicated to induce NFκB gene expression. Due to the …
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Mechanisms of 17-beta-estradiol regulation of the proto-oncogene Bcl-2 in MCF-7 human breast cancer cells.
… Bcl-2 expression is the tumour suppressor gene, p53. We investigated the effects of various mutant p53 proteins and low levels of p53 on Bcl-2 expression in MCF-7 cells. Neither MCF-7/E6 cells expressing virtually undetectable levels of p53 nor MCF-7/173L cells expressing a DNA binding domain …
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Comparison of wild-type and hotspot mutant p53 interactomes: The hunt for mutant-specific binding partners & Investigation and characterization of natural killer cell responses in genetically-engineered mouse models of non-small cell lung cancer
… in human cancer is the tumor suppressor gene p53, which is routinely found to have missense mutations at recurrent hotspot residues. Investigations of mutant p53 hotspot variants have suggested novel gain-of-function (GOF) traits, which can be driven through mutant-specific protein-protein …
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P53R245W Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer
<p><em>Trp53</em> mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of <em>Trp53</em> mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with …
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Modeling Cancer Using Li-Fraumeni Syndrome Patient-Derived Induced Pluripotent Stem Cells
… caused by germline mutations in the gene <em>TP53</em>, which predispose individuals to a wide range of malignancies, including osteosarcoma and breast cancer. In the previous study, our group developed a novel disease model platform by reprograming LFS patients' fibroblasts to induced …
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Functional analysis of ANKRD11 and FBXO31: two candidate tumour suppressor genes from the 16q24.3 breast cancer loss of heterozygosity region.
… cancer tumour suppressors. ANKRD11: a novel p53 coactivator involved in the rescue of mutant p53. The ability of p53 to act as a transcription factor is critical for its function as a tumour suppressor. Ankyrin repeat domain 11 (ANKRD11) was found to be a novel p53-interacting protein which …
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Interplay Between P53 and Epigenetic Pathways in Cancer
The human TP53 gene encodes the most potent tumor suppressor protein p53. More than half of all human cancers contain mutations in the TP53 gene, while the majority of the remaining cases involve other mechanisms to inactivate wild-type p53 function. In the first part of my dissertation research, I …
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Novel Cellular Targets of Aspirin in Chemoprevention studies on P53, G6PD and c-MYC
… lines. We investigated the effect of aspirin on p53, glucose 6-phosphate dehydrogenase (G6PD), and c-Myc, all of which are known to play a major role in cancer development. p53 is a tumor suppressor protein, often mutated in cancers causing its inactivation. Expression of G6PD is elevated in many …
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P53 Genes Act to Restrain Mobile Elements
Oncogenic stress provokes tumor suppression by p53 but the extent to which this regulatory axis is conserved remains unknown. Using a biosensor to visualize p53 action, we find that Drosophila p53 is selectively active in gonadal stem cells after exposure to stressors that destabilize the genome. …
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