The TP53 Gene and Its Role in Cancer

The TP53 gene is a gene that is mutated in many cancers. It is the most common gene mutation found in cancer cells. A tumor-suppressor gene, TP53 codes for a protein that inhibits the development and growth of tumors. A gene that has been coined "the guardian of the genome," when inactivated, it can also play a role in the persistence, growth, and spread of a cancer that develops.

The TP53 gene or its proteins are also referred to as tumor protein TP53, cellular tumor antigen TP53, phosphoprotein TP53, antigen NY-CO-13, or transformation-related protein 53.

Learn more below about the functions of TP53, how it works to stop cancer from forming, how is may be damaged, and therapies that may help to reactivate its effect.

Function of the TP53 Gene

There are two types of genes that are important in the development and growth of cancers: oncogenes and tumor-suppressor genes. Most often, an accumulation of mutations in both oncogenes and tumor-suppressor genes is responsible for the development of cancer.

Oncogenes vs. Tumor-Suppressor Genes

Oncogenes arise when normal genes present in the body (proto-oncogenes) are mutated, causing them to be activated (continually turned on). These genes code for proteins that control cell division. Their activation might be thought of as analogous to having the accelerator stuck in the down position in a car.

Tumor-suppressor genes, in contrast, code for proteins that function to repair damaged DNA (so a cell can't become a cancer cell), or result in the death (programmed cell death or apoptosis) of cells that can't be repaired (so they can't become a cancer cell). They may also have other functions important in cancer growth, such as playing a role in regulating cell division or angiogenesis (the growth of new blood vessels to feed a tumor). Using the analogy above, tumor-suppressor genes can be thought of as the brakes on a car.

Tumor-suppressor genes that many people are familiar with are the BRCA genes. BRCA gene mutations are known to be associated with the development of breast cancer and other tumors.

How the TP53 Gene Works to Prevent Cancer

TP53 is a protein whose main function is to repair DNA in order to prevent altered DNA from being passed on to daughter cells. When the damage in DNA is too extensive to be repaired, TP53 proteins signal cells to undergo programmed cell death (apoptosis).

Gain of Function

The TP53 gene is mutated in around 50% of cancer cells, but in addition to its role in tumor suppression, cancer cells themselves can find ways to inactivate and alter the gene, leading to new functions that help sustain the growth of a cancer. These are referred to as "gain-of-functions." Some of these gain-of-functions can include:

• Inducing resistance to cancer drugs
• Regulating metabolism (to give cancer cells an advantage over normal cells)
• Promoting spread of the tumor (metastases)
• Enhancing growth of the tumor
• Inhibiting apoptosis of cancer cells
• Inducing genomic instability
• Facilitating angiogenesis

An Analogy Describing the TP53 Gene

A very simplistic way to look at the TP53 gene would be to picture yourself as the TP53 gene, and a plumber as one of the proteins you can control. If you have a water leak and you are “functioning properly,” you would be able to make a phone call to the plumber. The plumber could then come to your home and either repair the leaky faucet, or you could remove it completely to stop the water leak. If you were unable to make the call (analogous to a faulty TP53 gene), the plumber would not be called, and the leak would continue (analogous to cancer cells dividing). In addition, you would not be able to turn off the water, which would eventually flood your home.

Once your home is flooding, the faucet may then take on a life of its own, preventing you from turning it off, preventing other plumbers from getting near, speeding up the flow of water, and adding new leaky pipes around your home, including some that aren't even connected to the initial leaky faucet.

TP53 Gene Mutations

A mutation in the TP53 gene (located on chromosome 17) is the most common mutation found in cancer cells and is present in over 50% of cancers. There are two primary types of gene mutations: germline and somatic.

Germline vs. Somatic Mutations

Germline mutations (heritable mutations) are the type of mutations people may be concerned with when wondering if they have a genetic predisposition to cancer. The mutations are present from birth and affect every cell in the body. Genetic tests are now available that check for several germline mutations that increase cancer risk, such as mutated BRCA genes. Germline mutations in the TP53 gene are uncommon and associated with a specific cancer syndrome known as Li-Fraumeni syndrome.

People with Li-Fraumeni syndrome often develop cancer as children or young adults, and the germline mutation is associated with a high lifetime risk of cancers, such as breast cancer, bone cancer, muscle cancer, and more.

Somatic mutations (acquired mutations) are not present from birth but arise in the process of a cell becoming a cancer cell. They are only present in the type of cell associated with the cancer (such as lung cancer cells), and not other cells in the body. Somatic or acquired mutations are by far the most common type of mutation associated with cancer.

How the TP53 Gene May Be Damaged (Inactivated)

The TP53 gene may be damaged (mutated) by cancer-causing substances in the environment (carcinogens) such as tobacco smoke, ultraviolet light, and the chemical aristolochic acid (with bladder cancer). Often times, however, the toxin leading to the mutation is unknown.

What Happens If the TP53 Gene Is Inactivated?

If the gene is inactivated, it no longer codes for the proteins that lead to the functions noted above. Thus, when another form of DNA damage occurs in another region of the genome, the damage is not repaired and may result in the development of cancer.

Cancers and TP53 Gene Mutations

TP53 gene mutations are present in around 50% of cancers overall, but are more commonly found in some types than others. Mutations in the TP53 gene have been one of the great challenges in cancer treatment, since these genes function to maintain stability of the genome. With a functioning TP53 gene, further mutations that both facilitate the growth of a cancer and confer resistance to treatments may occur.

Cancers Associated With TP53 Gene Mutations

There are a wide range of cancers associated with mutations in the TP53 gene. Some of these include:

• Bladder cancer
• Breast cancer (the TP53 gene is mutated in around 20% to 40% of breast cancers)
• Brain cancer (several types)
• Cholangiocarcinoma
• Head and neck squamous cell cancer
• Liver cancer
• Lung cancer (the TP53 gene is mutated in most small-cell lung cancers)
• Colorectal cancer
• Osteosarcoma (bone cancer) and myosarcoma (muscle cancer)
• Ovarian cancer
• Adrenocorticol carcinoma

Once Mutated, Always Mutated? Targeting the TP53 Gene

Due to the great importance TP53 mutations play in cancer, researchers have been looking for ways to reactivate the gene. Though the science is very complex, it is advancing, and small molecules known as MDMX inhibitors are now being evaluated in clinical trials for people with blood-related cancers.

This is an area in which dietary approaches may be exploited in the future as well. Unlike the strategy behind the small molecules noted (which inhibit the binding of MDM2 to TP53), phytonutrients in some plant-based foods may directly reduce MDM2 expression. A number of natural products have been found to alter expression either in the lab, with the particular natural product thought to work for different types of cancer. Examples include the flavonoid genistein in prostate and breast cancers, melatonin in breast cancer, and curcumin (a component of the spice turmeric) in prostate, lung, and breast cancers.

A Word From Verywell

The TP53 gene is a gene that, when mutated, plays a large role in many cancers. Attempts to reactivate the gene have been challenging, but science has reached the point where early clinical trials are looking at drugs that may impact its function. In addition, those who have promoted a healthy diet for people living with cancer may be encouraged by recent studies on natural products and TP53 gene function. That said, the evidence isn't nearly at the point at which researchers would make dietary recommendations.

It's also important to emphasize caution when it comes to these natural products. It wasn't long ago that, after finding that people who ate a diet rich in foods containing beta-carotene had a lower risk of lung cancer, researchers set out to study the potential effect of supplements of beta-carotene on risk. Unlike the reduced risk seen with dietary beta-carotene, however, beta-carotene in supplement form was associated with an increased risk of developing the disease.