Compare and Contrast Tumor Suppressor Genes and Proto-Oncogenes

Cancer is a genetic disease caused by certain changes to genes that control the way our cells function, especially how they grow and divide. Genes carry the instructions to make proteins, which do much of the work in our cells. Certain gene changes can cause cells to evade normal growth controls and become cancer. Genetic changes that promote cancer can be inherited from our parents if the changes are present in germ cells, which are the reproductive cells of the body (eggs and sperm). Such changes, called germline changes, are found in every cell of the offspring. In general, cancer cells have more genetic changes than normal cells. But each person’s cancer has a unique combination of genetic alterations.

Its locus is particularly amplified in these noted tumours leading to the progression of these cancers, it can be suppressed by p53 (tumour/ proliferation suppressor) which represses the EZH2 promoter, resulting inhibition of cell proliferation and invasion (Bracken, 2003; Xiao, 2011).

Cancer is a disease that has been an ongoing controversy on what can help to prevent getting it. Cancer is when cells are dividing at an uncontrollable rate. Cancer is developed when cancer cells go into lymph nodes and also when they take over the blood vessels, lymph nodes are when there is swelling the the lymphatic system. With the cancer there is swelling which is called a tumor. Tumor is when there is swelling in the part of the body that is not caused by inflammation, but is caused by a large group of abnormal tissue cells. There are two different types of tumors. There is the malignant tumor which is a tumor that can be cancerous which is when the cells divide at a faster rate, and can also take over tissues. The other tumor is a benign tumor, which is a noncancerous and could be removed, and it cannot take over any near tissues. Genes play a big role in cancer itself. Cancer happens when a gene is mutated and changed, and when the gene becomes mutated it becomes abnormal. Because it is not a normal cell, its a mutated cell which makes it more cancerous. One gene that is a cancerous cell is a proto-oncogene which is a normal gene, but if it is mutated or changed it becomes a oncogene which is then now a cancerous cell and then divides into multiple different cancerous cells that can affect one 's body. The proto-oncogene can escalate if mutated into a cancerous cell. Which

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008. The leading cause of cancer mortality in females is breast cancer, accounting for 23% followed by lung cancer and cervical cancer accounting for 11% respectively. Furthermore, estimates show that, the leading cause of cancer mortality in males is lung cancer accounting for 17% of the total new cancer cases and 23% in total cancer deaths. [2].

Under normal conditions, cells balance division and apoptosis, and these processes are accomplished and preserved by several biochemical “checkpoints” during the cell cycle2. When these checkpoints are affected, uncontrolled cellular proliferation and cancer can result. Two general classes of cancer genes are oncogenes and tumor suppressor genes. Oncogenes facilitate tumor formation by directly accelerating cell division, whereas tumor suppressor genes, when affected, allow uncontrolled growth that was normally suppressed2. Tumor suppressor gene loss usually affects a cell’s phenotype when both copies of the gene are lost, so null alleles can be present in a heterozygous state in cells without affecting cell and tissue phenotype. The loss of these genes can occur through genetic mutation or the epigenetic silencing of genes via promoter

Cancers seem to develop progressively. There will be intermediate stages between those normal cells and highly altered cells. Hyperplasia is the first stage in which cells look normal but with increased cell number. Next stage is dysplasia, characterized by more cytologically abnormal cells. Dysplasia is followed by metastasis stage, where cells can invade new tissues. During transformation from normal cells to altered cells, either inhibition of tumor suppressor gene or activation of anti-apoptotic genes happen. Almost in all cancers, cell cycles regulators are mutated. Main hallmarks of cancer include induction of angiogenesis, activation of the oncogene, suppression of apoptotic or tumor suppressor gene, activation

Tumor suppressor gene tells the when to die, repair the mistakes made in the DNA, and slow down cell division. If a tumor suppressor gene gets mutated the cells will grow out of control with nothing to stop them. The mutation can be caused when this gene isn’t activated. Two common example of a tumor suppressor are the p53 and NF1. Proto oncogenes codes for protein which helps with the cell cycle, prevents differentiation in cell, and programs cell death. If a proto oncogenes gets mutated there would be change in the protein sequence which would interfere normal cell regulations. The name of the proto oncogene was oncogene. DNA repair identifies incorrections and damages and fixes them. These three genes are mostly used to find cancer because

Cancer remains one of the most devastating diseases in the world. Tumor is the uncontrolled development and spreading of cells that may affect almost any tissue of the body. In this regard, more than 10 million individuals every year are determined to have cancer around the world (reference). It is evaluated that there will be 15 million new cases by the year 2020 (Reference). Around the world, every year cancer causes six million passings (12% of all deaths). Carcinogenesis is a multistep process regulated by genetic and epigenetic changes; disrupting several signaling pathways regulating cellular growth, apoptosis, differentiation and angiogenesis [1,2]. As a normal routine, mammalian cells grow, divide, and die in an orderly fashion. However,

Oncogenes is the result of when an proto-oncogene mutates. Proto-oncogenes is a gene that “codes for proteins that regulate cell growth and differentiation” (lecture

In the year 2016, the American Cancer Society projected that 595,690 individuals will pass due to cancer and 1,685,210 individuals will develop a new cancer case. Many scientists such as Dr. Bert Vogelstein or Dr. Robert Weinburg have been trying to understand the mechanism behind cancer and create therapeutic agents that could potentially prevent this disease from occurring. The most novel and studied gene and protein in regards to cancer is p53. The protein was discovered in the 1970s when research was focused on cancers that are caused by viruses and was later identified as being a tumor suppressor (1). One of the most studied areas of cancer is how p53 functions and its role in the cell cycle which has led to studies that target p53 as a therapeutic agent for cancer (1). In the year 2001, it was found that the protein product of the gene hSIR2SIRT1, which is a homolog of S. cerevisiae Sir2 protein, deacetylates the p53 protein and allows for either cell growth arrest or apoptosis (2). Due to this finding, the Sirtuin 1 protein has been heavily studied and even been targeted as being a therapeutic target for varying diseases and even involved in the phenomena known as caloric restriction (3–5). ¬

In recent years, the evidences show that this theory cannot be generalized. Significant evidence represented that the lack of only one allele in several tumor suppressor such as P53, PTEN, SMAD4 is sufficient to disable the synthesis of the gene product and may promote the tumorigenic process, called haploinsufficiency. In this case, tumor suppressor genes lead to tumorigenesis, without an inherited mutation in an allele.

Tumor progression or cancer development in humans takes decades to develop because this process requires multiple insults like mutations and epigenetic changes in the DNA. These changes

Invasions result in the destruction of healthy tissue among one’s central physique. Moreover, such invasive cells may even allow for the generation of capillary blood vessels from those that are existing as a source for their survival through the process of angiogenesis. The tissue and/or organ in which the tumor has derived from or originated allows for cancer classification and characterization. Derived from epithelial cells, carcinomas exist to be one of the most common forms of cancer that lead to mortality. For instance, the primary tumor that arises among the breast is also known as breast cancer, while metastatic cells derived from the female reproductive organ would be classified as gynecologic/ovarian cancer. Rather than by mere unfortunate chance, the metastasis of tumor cells is conceived by way of its growth environment and cell interactions. Among the most prevalent cancer incidences amidst women, these forbidding diseases arise typically on account of inherited genetic mutations [in BRCA1/BRCA2], as well as through the inevitable process of aging.

It was earlier thought that up to seven independent genetic hits are necessary for the development and progression of a malignant cancer[Fearon ER and Vogelstein B, 1990], but recent studies suggest that abnormal expression of only three genes might be sufficient for normal cells to convert to cancer cells [Hahn WC et al 1999]. In one such case (H-ras, hTERT, SV40LT) the cancer causing genes were all dominant and transformed proto oncogenes. Also, in this case inactivation of a single oncogene (e.g., mutant ras) can result in tumor regression which implies that in some cases (e.g., mutant ras) continuous expression of oncoproteins is functionally important, non-redundant and indispensable for sustained tumor growth despite a great number of genetic and epigenetic complexities associated with tumor formation. This phenomena is called “Oncogene Addiction” and it provides a rationale for targeted therapy. Thus, Oncogenes have attracted a great deal of interest as molecular targets for cancer therapy in recent years.

A more recent model of cancer, the CSCs Model, covers issues not completely explained by the Stochastic Theory, such as tumor recurrence after treatment. The CSCs Model states that surviving, transformed sub-clones that form part of tumors have SCs properties that allow them to drive tumor progression. The CSCs Model is unidirectional in that SCs-like cells may generate progenitor daughter cells (transit-amplifying cells) that in turn divide to produce differentiated (nontumorigenic) cells. Cellular heterogeneity within tumors depends on factors including the already mentioned branching mutation patterns and on cues from the TME. Thus, the TME can contribute to cell transformation