Why Tumor Suppressor Genes Are Important in Cancer

Tumor suppressor genes make proteins that regulate the growth of cells, and they play an important role in preventing the development of cancer cells.

When tumor suppressor genes are altered or inactivated due to a mutation (either one that is present at birth or one that occurs later in life), they make proteins that are less effective at controlling cell growth and/or repair. The result is unchecked growth of damaged or abnormal cells, which leads to uncontrolled growth and the development of cancerous tumors.

Tumor suppressor genes are also known as antioncogenes or loss-of-function genes.

Types of Tumor Suppressor Genes

Tumor suppressor genes come in three main types. Each type has a different function:

  1. Telling cells to slow down and stop dividing
  2. Repairing damage to cellular DNA that results from dividing and could lead to cancer
  3. Causing damaged cells to start a process called programmed cell death, or apoptosis

Oncogenes vs. Tumor Suppressor Genes

Two primary types of genes are involved in the development of cancer: oncogenes and tumor suppressor genes. The term oncogenes literally means "cancer genes," and these genes result in the uncontrolled growth of cells. (Proto-oncogenes are the genes that help cells grow, and when mutated so they function poorly are then referred to as oncogenes).

Tumor suppressor genes are easier to describe by using an analogy.

Analogy to Driving: Tumor Suppressor Genes are the Brakes

More and more, cancer research is delving into immunotherapy because of "on and off switches" for cancer that have been discovered. It can get highly technical and confusing, so it may help to think of cells as cars.

Each cell has an accelerator and brakes. In normal cars, both are working fine. Multiple processes make sure they stay in balance so the car both moves along steadily, but doesn't crash.

Cancer begins with a series of mutations in genes. Genes function as a blueprint for making proteins with different functions. Some mutations are no big deal—they ride along quietly and don't mess with anything. They're called passenger mutations.

Then we come to driver mutations. The driver can decide to go too fast or too slow, and it's these driver mutations that drive the growth of cancer cells.

Cancer can be related to problems with either the accelerator or the brakes, but often, damage to both oncogenes and tumor suppressor genes occurs before cancer develops. In other words, the accelerator has to be stuck to the floor AND the brakes have to malfunction. The fact that cancer often requires a number of different mutations is, in part, why cancer is more common in older people. More time allows for more mutations.

In this car analogy:

  • Oncogenes are the genes that control the accelerator
  • Tumor suppressor genes control the brakes

Using this analogy in reference to the different types of tumor suppressor genes listed above:

  • Some types are responsible for hitting the brakes
  • Some repair broken brakes
  • Others tow the car away when it can't be fixed

Inheritance and Oncogenes vs. Tumor Suppressor Genes

Several important differences exist between oncogenes and tumor suppressor genes in cancer.

In general, oncogenes are dominant. In our bodies, we have two sets of each of our chromosomes and two sets of genes: one from each of our parents. With dominant genes, only one of the two copies needs to be mutated or abnormal for a negative effect to occur.

Take, for example, brown eyes. If people inherit one copy of the brown-eyed gene and one copy of the blue-eyed gene, their eye color will always be brown. In the car analogy, it takes only one copy of a mutated gene controlling the accelerator for the car to run out of control (only one of the two proto-oncogenes needs to be mutated to become an oncogene).

Tumor suppressor genes, in contrast, tend to be recessive. That is, just like you need two genes for blue eyes in order to have blue-eyes, two suppressor genes must both be damaged in order to contribute to cancer.

It's important to note that the relation between oncogenes and tumor suppressor genes is much more complex than this, and the two are often intertwined. For example, a mutation in a suppressor gene may result in proteins that are unable to repair mutations in an oncogene, and this interaction drives the process forward.

Tumor Suppressor Genes and the "2 Hit Hypothesis"

Understanding the recessive nature of tumor suppressor genes can be helpful in understanding genetic predispositions and hereditary cancer.

Examples of tumor suppressor genes are the BRCA1/BRCA2 genes, otherwise known as the "breast cancer genes." People who have a mutation in one of these genes have an increased risk of developing breast cancer (among other cancers).

However, not everyone with the gene develops breast cancer. The first copy of these genes is mutated at birth, but it's not until another mutation occurs after birth (an acquired mutation or somatic mutation) that abnormal repair proteins are made that increase the risk of cancer.

It's important to note that there are several genes associated with the development of breast cancer (not just BRCA genes), for which genetic testing is available, and many of these are thought to be tumor suppressor genes.

This recessive nature is what is referred to in the "2 hit hypothesis" of cancer. The first copy (in the example above, the inherited copy of the defective gene) is the first hit, and a later mutation in the other copy of the gene later in life is the second hit.

Of note is that having "2 hits" alone is not enough to lead to cancer. Damage to DNA cells (from the environment or due to normal metabolic processes in cells) must then occur, and together the two mutated copies of the tumor suppressor gene are unable to create effective proteins to repair the damage.

Tumor Suppressor Genes and Hereditary Cancer

According to the American Cancer Society, inherited cancer syndromes account for between 5% and 10% of cancers, but studies suggest the percent of cancers that can be attributed to these genes may be much higher. Genetic screening is now available for several of these syndromes, but in many cases, a genetic predisposition cannot be found with testing. In this case, it's very helpful for people to work with a genetic counselor who may be able to understand more about risk based on family history.

Two Basic Roles of Tumor Suppressor Genes: Gatekeepers and Caretakers

As noted earlier, tumor suppressor genes may function as the "brakes" of the car in three primary ways but inhibiting cell growth, fixing broken DNA, or causing a cell to die. These types of tumor suppressor genes can be thought of as "gatekeeper" genes.

Yet some tumor suppressor genes function in more of a caretaker role. These genes create proteins that oversee and regulate many of the functions of other genes to maintain the stability of DNA.

In the examples below, Rb, APC, and p53 function as gatekeepers. In contrast, BRCA1/BRCA2 genes function more as caretakers and regulate the activity of other proteins involved in cell growth and repair.

Examples

Many different tumor suppressor genes have been identified, and it's likely that many more will be identified in the future.

History

Tumor suppressor genes were first identified among children with retinoblastoma. In retinoblastoma, in contrast to many tumor suppressor genes, the tumor gene that is inherited is dominant—and therefore allow cancers to develop in young children. If one parent carries the mutated gene, then 50 percent of their children will inherit the gene and be at risk for retinoblastoma.

Common Examples

Some examples of tumor suppressor genes associated with cancer include:

  • RB: The suppressor gene responsible for retinoblastoma
  • p53 gene: The p53 gene creates protein p53 which regulates gene repair in cells. Mutations in this gene are implicated in around 50 percent of cancers. Inherited mutations in the p53 gene are much less common than acquired mutations and result in the hereditary condition known as Li Fraumeni syndrome. The p53 codes for proteins that tell cells to die if they are damaged beyond repair, a process referred to as apoptosis.
  • BRCA1/BRCA2 genes: These genes are responsible for around 5 percent to 10 percent of breast cancers, but both BRCA1 gene mutations and BRCA2 gene mutations are associated with an increased risk of other cancers as well. (BRCA2 is also linked to an increased lung cancer risk in women.)
  • APC gene: These genes are associated with an increased risk of colon cancer in people with familial adenomatous polyposis.
  • PTEN gene: The PTEN gene is one of the non-BRCA genes that can increase the risk of a woman developing breast cancer (up to an 85 percent lifetime risk). It is associated with both PTEN hamartoma tumor syndrome and Cowden syndrome. The gene codes for proteins that aid in cell growth but also help cells stick together. When the gene is mutated, there is a greater risk that cancer cells will "break off" or metastasize.

At the current time, more than 1200 human tumor suppressor genes have been identified. The University of Texas has a tumor suppressor gene database that lists many of these genes.

Tumor Suppressor Genes and Cancer Treatments

Understanding tumor suppressor genes may also help explain a bit why therapies, such as chemotherapy, don't completely cure cancer. Some cancer treatments work to stimulate cells to commit suicide. Since some tumor suppressor genes trigger the process of apoptosis (cell death), when they aren't working properly, the cancer cells may not be able to go through the process of apoptosis as other cells might.

A Word From Verywell

Learning about the function of tumor suppressor genes and oncogenes involved in the formation of cancer, as well as the characteristics of cancer cells and how cancer cells differ from normal cells, can help researchers look at new ways to both identify people at risk of cancer and to treat cancers that occur.

Experts know it's not just the changes in the genomes themselves that matter, but modifying the way genes are expressed without genetic changes (known as epigenetics) plays a role in cancer. It's possible that changes in the environment of our tissues may affect the "expression" of tumor suppressor proteins made by these genes.

For example, one study looked at the role medicinal herbs may play in the activation of tumor suppressor molecules, and several other studies have looked at the role of dietary patterns in tumor suppressor activation.

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