The p53 Gene - It's Role in Cancer

What is P53 and What Role Does It Play in Cancer?

diagram of a strand of DNA
What is the p53 gene?. istockphoto.com

What is the p53 Gene?

What exactly is the p53 gene and what role does it play in the development and progression of cancer?

The p53 Gene is a Tumor Suppressor Gene

The p53 gene is a gene that codes for a protein that inhibits the development and growth of tumors (in addition to other functions). It is known as a tumor suppressor gene. If this gene is mutated—that  is, altered in some way by either the environment or inheritance, damaged cells are allowed to survive, and ultimately, develop into cancer cells.

 An example of tumor suppressor genes include BRCA2 which is important in the development of breast and other cancers.

p53 Gene Mutation is Common

A mutation in the p53 gene (located on chromosome 17) is the most common mutation found in cancer cells and is present in over 50% of cancers.

What Does the p53 Gene Do?

The p53 gene is responsible for proteins that can either repair damaged cells or cause damaged cells to die, a process called apoptosis. When the gene is not working due to a mutation, these proteins that repair cells or eliminate damaged cells are not produced, and abnormal cells are allowed to divide and grow.

A very simplistic way to look at the p53 gene would be to picture yourself as the p53 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 remove it completely to stop the water leak.

If you were unable to make the call (analogous to a faulty p53 gene), the plumber would not be called and the leak would continue (analogous to cancer cells dividing), and eventually flood your home.

In other words, the p53 gene functions as a safety net that prevents abnormal cells from developing into tumors in 3 primary ways (as of yet -- there is much we need to learn about p53.) by:

  • Fixing damages in DNA before damaged cells divide (and pass on the mistake.)
  • Causing apoptosis.  When the damage in DNA is too extensive to be repaired, tumor suppressor genes induced programmed cell death (apoptosis) so that the damage is not passed on.
  • P53 likely has many other functions, including effects on metabolism that play a key role in cancer growth.

What Causes Damage to the p53 Gene?

The p53 gene can be damaged (mutated) by cancer-causing substances in the environment, such as tobacco smoke. It may also be absent in some people from birth. People that inherit only one copy of the p53 gene (Li-Fraumeni syndrome) are predisposed to developing cancer later in life.

Importance of the p53 Gene in Lung Cancer

An understanding of the p53 gene and the proteins that it codes for may lead to better methods of diagnosing and treating lung cancer in the future.

Sources:

Demirhan, O. et al. Alternations in p16 and p53 genes and chromosomal findings in patients with lung cancer: Fluorescence in situ hybridization and cytogenetic studies. Cancer Epidemiology. 2010 May 3. (Epub ahead of print).

Farnebo, M. et al. The p53 tumor supprossor: a master regulator of diverse cellular processes and therapeutic target in cancer. Biochemical and Biophysical Research Communications. 2010. 396(1):85-9.

Hecht. S. Progress and challenges in selected areas of tobacco carcinogenesis. Chemical Research in Toxicology. 2008. 21(1):160-71.

Meek, D. Regulation of the p53 response and its relationship to cancer. Biochemical Journal. 2015. 469(3):325-46.

Muller, P., and K. Vousden. p53 mutations in cancer. Nature Cell Biology. 2013. 15(1):2-8

Pfeifer, G. and A. Besaratinia. Mutational spectra of human cancer. Human Genetics. 2009. 125(5-6):493-506.

Wang, X., Simpson, E., and K. Brown. p53: Protection against Tumor Growth beyond Effects on Cell Cycle and Apoptosis. Cancer Research. 2015 Nov 16. (Epub ahead of print).

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