Non-Cell Autonomous Tumor Supression by p53

The purpose of this research was to determine the mechanisms in naked mole-rats that restricts cell proliferation and tumor formation. Contact inhibition is a mechanism observed where cell proliferation stops when two cells come in contact with one another. This process is caused by elevated levels of p27 cyclin-dependent kinase inhibitor which stops cells in the G1 phase from dividing. The cylcin-dependent kinase inhibitor p16 is also thought to regulate contact inhibition but its levels do not change in mice or human samples. Tumor-suppressor genes Rb and p53 are present in high concentration during contact inhibition to help control cell proliferation and apoptosis respectively. It was hypothesized that the naked mole-rats' cancer resistivity

Besides inducing apoptosis and controlling the cell cycle, p53 has been demonstrated to be a central component and key regulator of the metabolic stress machinery. The metabolic balance between glycolysis and oxidative phosphorylation is heavily coordinated by p53 activity, which is activated by

In the book p53: The Gene That Cracked The Cancer Code by Sue Armstrong, they focus on statistics rather than a story. This book describes the change throughout time while focusing on the p53 gene. It talks about different genes that affect p53 and how cancer can happen.

Cancer known in medicine as a malignant neoplasm is one of the biggest killers worldwide. In 2007, cancer caused roughly 13% (7.9 million) of the planet’s deaths (Jemal, 2011). This will more greatly affect an aging society such as ours in years to come, and yet it is already the foremost cause of death in the developed world. The main reason cancer causes so many fatalities the body’s inability to mount an effective response to the failure of DNA replication within the body. This results in a mass

The ability of p53 to regulate metabolism is also associated with the ability to regulate cellular ROS levels. As previously mentioned, p53 can either remove damaged cells that have suffered sustained oxidative stress, or limit levels of ROS in order to lower oxidative stress and consequently, potential cell damage. Through the regulation of carbohydrate and lipid metabolism, p53 is able to influence the response to ROS accordingly. By driving the expression of TIGAR and promoting PPP activity, p53 can increase the production of NAPDH, which can be used to generate the cellular antioxidant GSH (Bensaad 2006). Moreover, at the expense of nucleotide synthesis, p53 can also promote GSH synthesis following serine starvation, thereby lowering ROS

The P53 prevents cancer formation by acting as a tumour suppressor gene. Also known as the TP53. It plays important roles in multicellular organisms by stopping genome mutations. The name p53 was established in 1979 describing the molar mass indicating that it is a 53kDa protein. It was first discovered in 1979 and was thought to be an oncogene (a gene capable of transforming regular cells into tumour cells). However in 1989 further research by Bert Vogelstein from John Hopkins School of medicine discovered that it was actually a tumour suppressor gene. The p53 protein consists of 393 amino acids. This protein can activate other proteins that have the ability to fix

Transformation-Related Protein 53, also known as TP53, is a tumor suppressor gene. It is named after its molecular mass. The gene was discovered by Arnold Levine, David Lane, and William Old in 1979 and was voted molecule of the year by science magazine in 1993. Although, it was not until 1989 that it was revealed to be a tumor suppressor gene. It was previously thought of as an oncogene. TP53 encodes for a protein, called p53 protein, that helps to regulate the cell cycle and inhibits mutations in the genome as well. Both of these functions help to conserve stability. One of the reasons for TP53’s high importance, and the extensive research on the gene, is its function to suppress cancer cells in multicellular organisms, including humans (Vijayaraj).

The level of activity of Gli genes, and thus Hh-pathway activation, determines skin tumor phenotype: high level signaling is shown to result in BCC and low-level signaling is shown to result in follicular derived tumors such as basaloid follicular hamartoma (BFH) (2). Gli2 is involved in the expression of cell cycle regulation genes in the Shh-pathway such as E2F1, CCND1, CDC2 and epidermal differential genes. Over-expression of Gli2 causes the up-regulation of such cell cycle regulation genes in developing hair follicles. Shh-activation most specifically promotes degradation of the p53 tumor suppressor gene (2), thus repressing transcription of p21, a key suppressor of cyclin E in cell-cycle regulation. Thus, G1 arrest is overrode, and the inability to control cell cycle is promoted: a key feature of cancer. Sufu and Kif7 have overlapping functions in regulating Gli transcription factors. Specifically, Gli2 forms a complex with Sufu to prevent transcriptional activity via preventing accumulation of Gli2 transcriptional factors into the nucleus, thus repressing Hh pathway transduction (3). Sufu also plays a role in stabilizing Gli2 by blocking Spop, an E3 ligase involved in degradation of Gli2 (3). In keratinocytes, Kif7

More than four thousands mutations of p53 genes have been identified in human tumors. p53 mutation in human skin cancers is consider to be unique mutation among other cancers mutations. p53 mutation in human skin cancers is mostly found to be C to T transitions. These transitions are located on dipyrimidine sites that are the specific target for UV radiation (Dumaz et. al, 1997). Alteration of tumor suppressor gene p53 will hinder p53 to repair damaged DNA or perform apoptosis as needed, which then results in precancerous cell (Madan et. al,

The Macrophage cell is a part of the Immune system (the immune system protect your body from virus, bacteria and pathogens) The word microphage actually means big eater. The job of the Macrophage is to inform other cell in the immune system (mainly the natural killer cells) that there is virus and bacteria or pathogen, then the immune system will come to kill the bacteria or virus. Macrophages will join the fight against foreign bodies by digesting enemies by process called Phagocytosis. It is broken down into a couple of steps:

The gene most associated with HCC is the TP53 gene, which is a tumor suppressor gene universal among many cancers. The p53 protein, when turned off, can mistakenly cause cancer since they are normally turned on (Rhine 4). When normal, the TP53 gene assures that cells do not grow beyond where the should, meaning they have anchorage dependence and density dependent inhibition. When damaged, abnormal cells and the formation of HCC can occur since the P53 protein is involved in cell cycle functions and apoptosis, because it does not stop the cells from accumulating mutations over time if its function is degraded (¨“Do We Know [...]?¨, Debuire and Lemoine). This tumor suppressor gene follows Mendelian rules, meaning they are recessive and must

The tumor suppressor gene p53 is any variant of a protein that is prearranged by homologous genes in a variety of organisms. The tumor suppressor gene is essential in multicellular organisms due to its function of preventing cancer development, therefore giving its identity of being a “tumor suppressor”. In the year 1979, the protein p53 was discovered bound to the T antigen found in the simian virus (SV40). Because it was found exceptionally in its mutant form, it was first thought of being an oncogene; it was not until ten years later that the protein was determined to be a crucial aspect in tumor suppression.

3.2 The macrophages were plated at 18,000cells/cm2. Again to obtain the best result on the antibody and flow cytometric techniques, the cell concentration needs to be sufficient.

P53 mutations are frequently found in solid tumors, such as lung, colon and head cancers, that are quite resistant to conventional therapies.

Protein p53 is regarded as the “genome guardian”, since it controls the cell cycle, avoiding abnormal growth finding in cancerous diseases [34,37]. Positive immunoexpresion of p53 is considered abnormal, due to its short-life to be detected in samples. The detection of this tumour-suppressor gene indicates mutation and loss of function, facilitating cancer formation. Mutation of p53 can occur by different processes and, especially in skin cancers, UV radiation is considered the most important associated mutagenic factor of skin cells. In addition, some viral infections, can also play a role in carcinogenesis due to viral binding on this gene [34,37]. UV radiation initiates tumorigenesis by inducing mutations in the p53 tumor suppressor gene [34,37,71,72]. As UV exposition increases mutation rates of this genomic guardian, [34,37] it was expected that OSCC would have a high prevalence of p53 immunoexpression. The association between OSCC in cattle and p53 mutations were previously studied. In one study, p53 were positive