How does an oncogene affect the development of cancer

Mutations may also occur in a regulatory or promoter region near the proto-oncogene. There are two types of genes that when mutated or otherwise changed, can increase the risk that cancer will develop: oncogenes and tumor suppressor genes. A combination of changes in both of these genes is frequently involved in the development of cancer.

Even when DNA damage such as point mutations occur to convert a proto-oncogene to an oncogene, many of these cells are repaired. Another type of gene, tumor suppressor genes, code for proteins that function to repair damaged DNA or eliminate damaged cells. These proteins can help reduce the risk of cancer even when an oncogene is present.

If mutations in tumor suppressor genes are also present, the likelihood of cancer developing is greater as abnormal cells are not repaired and continue to survive instead of undergoing apoptosis programmed cell death.

There are several differences between oncogenes and tumor suppressor genes:. Most often autosomal dominant, meaning that only one copy of the gene needs to be mutated to elevate cancer risk. Most often but not always autosomal recessive, a mutation in both copies must occur before it increases the risk of developing cancer. As noted earlier, cancer usually begins following an accumulation of mutations in a cell including those in several proto-oncogenes and several tumor suppressor genes. At one time it was thought that activation of oncogenes resulting in out-of-control growth was all that was necessary to transform a normal cell to a cancer cell , but we now know that other changes are most often needed as well such as changes that prolong survival of deranged cells.

These changes not only lead to cells that grow and divide uncontrollably, but that also fail to respond to normal signals for cells to die, fail to respect boundaries with other cells lose contact inhibition , and other characteristics that cause cancer cells to behave differently than normal cells. A few types of cancer, however, are associated with only single-gene mutations, with an example being childhood retinoblastoma caused by a mutation in a gene known as RB1.

Talking about mutations and cancer can be confusing because there are two different types of mutations to consider. Oncoproteins are the product the proteins that are coded for by oncogenes and are produced when the gene is transcribed and translated the process of "writing down the code" on RNA and manufacturing the proteins. There are many types of oncoproteins depending on the specific oncogene present, but most work to stimulate cell growth and division, inhibit cell death apoptosis , or inhibit cellular differentiation the process by which cells become unique.

These proteins can also play a role in the progression and aggressiveness of a tumor that is already present. The concept of oncogenes had been theorized for over a century, but the first oncogene was not isolated until when an oncogene was discovered in a cancer-causing virus called the rous sarcoma virus a chicken retrovirus. The majority of cancers, however, do not arise in relation to an infectious organism, and in many cellular oncogenes were found to be mutated proto-oncogenes; genes normally present in humans.

Since that time much has been learned about how these genes or the proteins they code for function, with some of the exciting advances in cancer treatment derived from targeting the oncoproteins responsible for cancer growth.

Different types of oncogenes have different effects on growth mechanisms of action , and to understand these it's helpful to look at what is involved in normal cell proliferation the normal growth and division of cells.

Most oncogenes regulate the proliferation of cells, but some inhibit differentiation the process of cells becoming unique types of cells or promote survival of cells inhibit programmed death or apoptosis. Recent research also suggests that proteins produced by some oncogenes work to suppress the immune system, reducing the chance that abnormal cells will be recognized and eliminated by immune cells such as T-cells.

While there are more than different functions of oncogenes, they can be broken down into several major types that transform a normal cell to a self-sufficient cancer cell. It's important to note that several oncogenes produce proteins that function in more than one of these areas. Some cells with oncogenes become self-sufficient by making synthesizing the growth factors to which they respond. The increase in growth factors alone doesn't lead to cancer but can cause rapid growth of cells that raises the chance of mutations.

Increased PDGF is present in many cancers, particularly bone cancer osteosarcoma and one type of brain tumor. Oncogenes may activate or increase growth factor receptors on the surface of cells to which growth factors bind. One example includes the HER2 oncogene that results in a significantly increased number of HER2 proteins on the surface of breast cancer cells. Other oncogenes affect proteins involved in transmitting signals from the receptor of the cell to the nucleus.

BRAF in melanoma is also in this category. Non-receptor protein kinases are also included in the cascade that carries the signal to grow from the receptor to the nucleus. A well-known oncogene involved in chronic myelogenous leukemia is the Bcr-Abl gene the Philadelphia chromosome caused by a translocation of segments of chromosome 9 and chromosome When the protein produced by this gene, a tyrosine kinase, is continually produced it results in a continuous signal for the cell to grow and divide.

Transcription factors are proteins that regulate when cells enter, and how they progress through the cell cycle. An example is the Myc gene that is overly active in cancers such as some leukemias and lymphomas. Cell cycle control proteins are products of oncogenes that can affect the cell cycle in a number of different ways.

Oncogenes may also produce oncoproteins that reduce apoptosis programmed cell death and lead to prolonged survival of the cells. Some oncogenes work like putting your foot down on the accelerator of a car, pushing a cell to divide. Other oncogenes work like removing your foot from the brake while parked on a hill, also causing the cell to divide. Within every cell in our body is a class of genes known as proto-oncogenes.

Proto-oncogenes play important roles in controlling cell division and cell death during our growth and development. However, if a proto-oncogene becomes mutated, or the cell makes extra copies of the proto-oncogene, it can become hyper-activated and lead to the appearance of uncontrolled cell division.

The inactivation of tumor suppressor genes and the activation of oncogenes together lead to the cancerous transformation of cells, and ultimately the formation of tumors. If you compare a normal cell to a car driving towards a tumor, the oncogene is equivalent to the accelerator, and the tumor suppressor gene is equivalent to the brake. When the cancer-causing gene mutation is activated, the cells accelerate to become cancerous, similar to a car with a gas pedal; when the tumor suppressor gene mutation is inactivated, it cannot inhibit cell canceration, which is similar to a car with a brake failure.

The activation of oncogenes and the inactivation of tumor suppressor genes are similar to a car with accelerator and brake failure. As a result, it quickly drives toward the end of cancer. As mentioned earlier, abnormalities in tumor cells are caused by genetic mutations.

In fact, in one generation of cells, the probability of mutation is very low; in addition, cell cancer requires multiple mutations such as oncogenes and tumor suppressor genes, so the probability of tumor occurrence is even lower. A hereditary tumor is because it has a mutated gene, which is equivalent to reducing an obstacle to tumor occurrence, thus greatly increasing the probability of tumor occurrence. In addition, there is another way to accelerate the process of tumorigenesis: that is, increase the frequency of mutations!

Xeroderma pigmentosum XP is a disease that increases the frequency of mutations to increase the probability of cancer. XP patients are very sensitive to ultraviolet radiation and can easily cause skin cancer in the irradiated area.

In normal people, this type of damage can be repaired by a type of DNA repair protein; and XP patients have defects in this type of protein, so they cannot repair the DNA damage caused by UV radiation. As a result, people discovered another type of genes related to tumor formation: DNA damage repair genes. DNA damage repair genes are theoretically neither oncogenes nor tumor suppressor genes. The normal DNA damage repair system can repair a variety of DNA damages, including those caused by mutagens and carcinogens in the environment.