a) Stimulate cell growth
b) Inhibit apoptosis
c) Stimulate cell division
d) Repair DNA damage
D is correct. Tumor suppressor genes are normal genes found in cells that function to stimulate apoptosis and inhibit cell division and cell growth.
These genes are also activated when DNA repair mechanisms in the cell fail to repair errors in the DNA molecule, such as mutations or structural damage. Moreover, tumor suppressor genes can become mutated, through “loss of function” mutations, which can result in the loss of some or all of their functions. If the tumor suppressor gene can no longer do its job, the cell can no longer induce apoptosis, inhibit cell growth and division or repair damaged DNA. These changes, along with other mutations in the cell, can potentially lead to the development of cancer.
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Several features of cancer are essential to understand for the MCAT exam. Figure 1 shows the different features of cancer and how they relate to one another.
Firstly, cancer growth signals are self-sufficient. Typically, for cells to grow and divide, they need signals telling them to do so. However, cancer cells produce growth signals on their own, which allows them to grow and divide uncontrollably.
Second, cancer cells are insensitive to anti-growth signals. When healthy cells grow or divide up to a certain point, they will receive signals that instruct them to stop growing and dividing. Cancer cells are insensitive to such signals, and this allows them to keep growing and dividing.
Third, cancer cells can invade and metastasize into other tissues. They can migrate and travel through the blood vasculature and spread to other organs. If a primary tumor is left untreated long enough, the secondary tumors will start to form in other regions of the body.
Fourth, cancer cells have unlimited replication potential. Most cells in the body can only replicate a fixed number of times. However, this is not the case for cancer cells. Cancer cells are virtually immortal in that they can replicate indefinitely.
Fifth, cancer cells can grow new blood vessels to sustain themselves (termed angiogenesis). Cancer cells proliferate and divide rapidly, so they are in constant need of nutrients and a method to eliminate metabolic waste products. In this way, they require the growth of new blood vessels to support themselves.
Lastly, cell death or apoptosis is inhibited in cancer cells. Healthy cells can defend themselves or eliminate damaged cells that may become cancerous by initiating cell apoptosis. Cancer cells inhibit apoptosis so that they can continue to grow and divide.
It is important to note that cancer does not create new genes. Instead, it works on pre-existing genes. In normal cells, there are genes called proto-oncogenes, which are normal genes that function to stimulate cell division, inhibit cellular differentiation, and halt apoptosis. These functions are the normal functions of proto-oncogenes found in healthy cells. However, proto-oncogenes can become mutated. These mutations are known as gain of function mutations, and they can increase the activity of the proto-oncogenes or cause them to lose their regulation.
In this way, proto-oncogenes are converted into oncogenes, and all of their activities become permanently activated. At this point, the gene will constantly stimulate cell division, inhibit cellular differentiation, and halt apoptosis. As previously stated, these are all features of cancer cells.
It is important to note that when proto-oncogenes are converted into oncogenes, they have the potential to cause cancer. The cell usually has multiple ways to protect from uncontrolled cell growth and cell division. Thus, with most types of cancer, it usually takes multiple mutations before a cell becomes cancerous. Some examples of cancers caused by oncogenes include breast cancer, gastrointestinal cancer, pancreatic cancer, lung cancer, thyroid tumors, and lung cancer.
Tumor suppressor genes, like proto-oncogenes, are normal genes found in the cell. Tumor suppressor genes function to stimulate apoptosis and inhibit uncontrolled cell division and cell growth. Furthermore, these genes are often activated when DNA repair processes fail to correct errors. For example, if there is a DNA mutation, DNA repair processes are initiated that try to fix those mutations. If this process fails, then tumor suppressor genes become activated to stimulate apoptosis.
However, if tumor suppressor genes become mutated due to loss of function mutations, then they can no longer do their job. This is another way that cancer can form, since the cell is no longer able to stimulate apoptosis and inhibit cell growth and cell division.
Interestingly, the most frequently mutated tumor suppressor gene in human cancer is the p53 gene. Over 50% of cancers carry a loss of function mutation in the p53 gene. Some examples include breast cancer, colon cancer, and liver cancer. In most cases of cancer, there is a combination of gain of function mutations that produce oncogenes and loss of function mutations that mutate tumor suppressor genes.
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