Friday 25 July 2003
Definition: PTEN is a tumor suppressor gene that is frequently deleted or mutated in prostate, endometrial and breast cancer. This lipid phosphatase regulates cell survival, growth and migration.
PTEN suppresses phosphoinositol-3-kinase (PI3K) signaling, thereby down-regulating downstream mediators, including the oncogenic serine-threonine kinase AKT, which in turn regulates the mTOR (mammalian target of rapamycin) growth pathway.
PTEN activity causes cell-cycle arrest and apoptosis as well as inhibition of cell motility. It has been proposed that PTEN blocks the cell cycle by increasing the transcription of the p27 Cip/Kip cell-cycle inhibitor and stabilizing the protein.
As the primary phosphatase of phosphatidylinositol (3,4,5)-trisphosphate, PTEN has a central role in reigning in the phosphoinositide 3-kinase (PI 3-kinase) network to control cellular homeostasis.
regulation of basic cellular functions
- cell migration
- cell size
- contractility of cardiac myocytes
Phosphatase and tensin homologue, deleted on chromosome 10 (PTEN) gene, mapped on chromosome 10q23, is frequently deleted in many human cancers but at particularly high frequency in endometrial carcinomas and glioblastomas. With loss of PTEN, therefore, cells are released into the cell cycle.
Mutations of the PTEN gene cause a dysregulation of the phosphoinositol-3-kinase/Akt pathway. The tumor suppressor properties of Pten are closely related to its inhibitory effect on the phosphatidyl-inositol-3’-kinase (Pi3k)-dependent activation of protein kinase B (Akt) signalling.
- Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum)(MIM.158350)
- autosomal recessive VATER association with hydrocephalus (MIM.276950)
- Proteus syndrome (MIM.176920)
- PTEN-associated tumor syndromes
- Cowden disease (MIM.158350) (80%)
- Bannayan-Zonana syndrome or Bannayan-Ruvalcaba-Riley syndrome (BRRS) (MIM.153480) (60%)
somatic mutations in cancer
- endometrial adenocarcinoma
- prostatic adenocarcinoma
- mammary adenocarcinoma
- malignant melanoma
- glioblastoma (24%)
- epidermoid carcinoma of head and neck
- Loss of PTEN/MMAC1 activity is a rare and late event in the pathogenesis of Wilms tumor (nephroblastoma) (20381115)
- PTEN loss is associated with upgrading of prostate cancer from biopsy to radical prostatectomy. (24993522)
- Loss of PTEN expression is associated with increased risk of recurrence after prostatectomy for clinically localized prostate cancer. (22684219)
Immunohistochemical staining of thyroidectomy specimens for PTEN can aid in the identification of patients with Cowden syndrome. (21921783)
PTEN loss is associated with upgrading of prostate cancer from biopsy to radical prostatectomy. Lotan TL, Carvalho FL, Peskoe SB, Hicks JL, Good J, Fedor HL, Humphreys E, Han M, Platz EA, Squire JA, De Marzo AM, Berman DM. Mod Pathol. 2015 Jan;28(1):128-37. doi : 10.1038/modpathol.2014.85 PMID: 24993522
Loss of PTEN expression is associated with increased risk of recurrence after prostatectomy for clinically localized prostate cancer. Chaux A, Peskoe SB, Gonzalez-Roibon N, Schultz L, Albadine R, Hicks J, De Marzo AM, Platz EA, Netto GJ. Mod Pathol. 2012 Jun 8. PMID: 22684219
Immunohistochemical staining of thyroidectomy specimens for PTEN can aid in the identification of patients with Cowden syndrome. Barletta JA, Bellizzi AM, Hornick JL. Am J Surg Pathol. 2011 Oct;35(10):1505-11. PMID: 21921783
Deletion of Pten in the mouse enteric nervous system induces ganglioneuromatosis and mimics intestinal pseudoobstruction. Puig I, Champeval D, De Santa Barbara P, Jaubert F, Lyonnet S, Larue L. J Clin Invest. 2009 Nov 2. PMID: 19884655
Eng C. PTEN: one gene, many syndromes. Hum Mutat. 2003 Sep;22(3):183-98. PMID: 12938083
Wishart MJ, Dixon JE. PTEN and myotubularin phosphatases: from 3-phosphoinositide dephosphorylation to disease. Trends Cell Biol. 2002 Dec;12(12):579-85. PMID: 12495846
Ali IU. Gatekeeper for endometrium: the PTEN tumor suppressor gene. J Natl Cancer Inst. 2000 Jun 7;92(11):861-3. PMID: 10841815