PTEN (gene)

Overview
PTEN (Phosphatase and Tensin homolog) gene is a human gene that acts as a tumor suppressor gene, which means that the protein encoded by this gene helps regulate the cycle of cell division by keeping cells from growing and dividing too rapidly or in an uncontrolled way. Mutations of this gene cause multiple advanced cancers.

The corresponding PTEN protein is found in almost all tissues in the body. The PTEN protein modifies lipids (fats) in cells by removing phosphate groups (clusters of one phosphorous and three oxygen atoms), making the PTEN protein a type of enzyme called a phosphatase. More specifically it is a phosphodiesterase and an inhibitor of the phospho-AKT pathway by removing the 3' phosphate group of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P3).

The structure of PTEN (solved by X-ray crystallography) reveals that it consists of a phosphatase domain, and a C2 domain: the phosphatase domain contains the active site which carries out the enzymatic function of the protein, whilst the C2 domain allows PTEN to bind to the phospholipid membrane so it is able to de-phosphorylate (PtdIns (3,4,5)P3) When the PTEN enzyme is functioning properly, it acts as part of a chemical pathway that signals cells to stop dividing and causes cells to undergo programmed cell death (apoptosis) when necessary. These functions prevent uncontrolled cell growth that can lead to the formation of tumors. There is also evidence that the protein made by the PTEN gene may play a role in cell movement (migration) and sticking (adhesion) of cells to surrounding tissues.

PTEN is one of the most commonly lost tumour suppressors in human cancer. During tumor development, mutations and deletions of PTEN occur that inactivate its enzymatic activity leading to increased cell proliferation and reduced cell death. Frequent genetic inactivation of PTEN occurs in glioblastoma, endometrial cancer, prostate cancer, and reduced expression is found in many other tumor types such as lung and breast cancer.

Related conditions
PTEN mutation also causes a variety of inherited predispositions to cancer.

Cowden syndrome: Researchers have found more than 70 mutations in the PTEN gene in people with Cowden syndrome. These mutations can be changes in a small number of base pairs or, in some cases, deletions of a large number of base pairs. Most of these mutations cause the PTEN gene to make a protein that does not function properly or does not work at all. The defective protein is unable to stop cell division or signal abnormal cells to die, which can lead to tumor growth, particularly in the breast, thyroid or uterus.

Other disorders: Mutations in the PTEN gene cause several other disorders that, like Cowden syndrome, are characterized by the development of noncancerous tumors called hamartomas. These disorders include Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like syndrome. Together, the disorders caused by PTEN mutations are called PTEN hamartoma tumor syndromes, or PHTS. Mutations responsible for these syndromes cause the resulting protein to be nonfunctional or absent. The defective protein allows the cell to divide in an uncontrolled way and prevents damaged cells from dying, which can lead to the growth of tumors.