Pten gene

PTEN is a gene localized on chromosome 10 (gene locus Chr 10: 87.86 - 87.97) that encodes a protein of the same name, a multifunctional lipid phosphatase of 403 amino acids.

PTEN is a tumor suppressor gene involved in the regulation of apoptosis and cycle arrest in the mTOR (mammalian target of rapamycin) pathway. Under normal conditions, it reduces the growth and survival of cells. In recent decades, numerous diseases have been linked to PTEN mutations in the germline, including

• Cowden syndrome
• Bannayan-Riley-Ruvalcaba syndrome
• Lhermitte-Duclos disease in adults
• macrocephaly-autism syndrome1 and
• SOLAMEN syndrome (segmental overgrowth, lipomatosis, arteriovenous malformation and epidermal nevus syndrome).

All syndromes are associated with mental retardation, overgrowth and a predisposition to tumors. These manifestations often overlap and the diseases are grouped together under the umbrella term PTEN hamartoma tumor syndromes (PHTS).

The protein encoded by the PTEN gene is an enzyme, PTEN phosphatase.

This phosphatase is an eminently important multifunctional enzyme. It catalyzes the hydrolytic cleavage of phosphoric acid esters (phospholipids and phosphoproteins) on various proteins and lipids. This regulates essential functions of these molecules.

Examples include the membrane lipid phosphatidylinositol-3,4,5-trisphosphate (PIP3) and other signal transducing molecules such as PIP2, PIP1, PIP4 and AKT1.

For example, PIP3 interacts With various molecules that are components of different signaling pathways and regulate cell proliferation, migration, and adhesion. PEN-catalyzed dephosphorylation of the molecules has an inhibitory effect on these signaling pathways.

Through these fundamental interventions in cellular signaling pathways, PEN presents itself as an essential player in signal transduction. Activated PTEN interrupts the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphatidylinositol phosphates (especially IP3), thereby enhancing apoptosis and acting as a tumor suppressor.

The growth of superfluous cells is suppressed.

The cell cycle is interrupted in the G1 phase.

Mutations in the PTEN gene can lead to functional defects of PTEN phosphatase. They can induce uncontrolled cell proliferation, thus also tumor growth.

Rare heterogeneous syndromes caused by autosomal dominant mutations of the PTEN gene are associated with tumors and are grouped as PTEN hamartoma tumor syndromes (Pilarski R et al (2019). PHTS patients tend to have tumor manifestations such as breast carcinomas, thyroid carcinomas, tumors of the endometrium and colon. A well-known example is Cowden syndrome.

Furthermore, there is a risk for immunological dysregulations and immunodeficiencies (Eissing M et al.2019).

1. Eissing M et al (2019) PTEN Hamartoma Tumor Syndrome and Immune Dysregulation. Translated Oncol 12:361-367.
2. Golas MM et al(2019) Looking for the hidden mutation: Bannayan-Riley-Ruvalcaba syndrome caused by constitutional and mosaic 10q23 microdeletions involving PTEN and BMPR1A. At J Med Genet 179:1383-1389.
3. Pilarski R et al (2019) PTEN Hamartoma Tumor Syndrome: A Clinical Overview. Cancers (Basel)11:6