● Enzyme Number (IUBMB): EC 220.127.116.11, EC
18.104.22.168, EC 22.214.171.124
Gene locus :
Phosphatase and tensin homolog
403 amino acids; about 47 kDa
PTEN acts as a dual-specificity protein
phosphatase, dephosphorylating tyrosine-, serine- andthreonine-phosphorylated proteins. It also
acts as a lipid phosphatase, an activity that is critical for its tumor suppressor
function. By negatively regulating intracellular levels of
phosphatidylinositol-3,4,5-trisphosphate in cells, PTEN antagonizes the
PI3K-AKT/PKB signaling pathway, thereby modulating cell cycle progression and
Germinal PTEN mutations have been
documented in Cowden disease and in Bannayan-Riley-Ruvalcaba phenotype; they
are observed along the various exons of the gene except the 9th (never
described) and the 1st (very few reports); a mutational hot spot is observed in
exon 5 (amino acids 130-131 and 173) in relation with the catalytic core motif;
in the great majority of the cases, inactivating mutations are observed, either
by protein truncation, or by “missense” mutation within the phosphatase domain.
Somatic PTEN mutations are observed in
several tumor types, notably those affecting vulva, endometrium, salivary
glands, CNS (glioma), prostate, skin (malignant melanoma); they lead to a
biallelic inactivation of the gene either by homozygous deletion, or by a
combination of point mutation (mainly substitution) and a large deletion of the
second allele. As with germinal mutations, mutational hot spots correspond to
aminoacids 130-131 and 173.
Defects in PTEN are a cause of Cowden
disease (CD), which is an autosomal dominant cancer predisposition syndrome
associated with elevated risk for tumors of the breast, thyroid and skin. The
predominant phenotype for CD is multiple hamartoma syndrome, in many organ
systems including the breast (70% of CD patients), thyroid (40-60%), skin, CNS
(40%), gastrointestinal tract. Affected individuals are at an increased risk of
both breast and thyroid cancers. Trichilemmomas (benign tumors of the hair
follicle infundibulum), and mucocutaneous papillomatosis (99%) are hallmarks of
Defects in PTEN are the cause of
Lhermitte-Duclos disease (LDD), which is characterized by dysplastic
gangliocytoma of the cerebellum which often results in cerebellar signs and
seizures. LDD and CD seem to be the same entity, and are considered as
Defects in PTEN are a cause of
Bannayan-Zonana syndrome (BZS), also known as Bannayan-Riley-Ruvalcaba syndrome
(BRRS). In BZS there seems not to be an increased risk of malignancy. It has a
partial clinical overlap with CD. BZS is characterized by the classic triad of
macrocephaly, lipomatosis and pigmented macules of the gland penis.
Defects in PTEN are a cause of Proteus
syndrome. Proteus syndrome is a hamartomatous disorder characterized by
overgrowth of multiple tissues, connective tissue and epidermal naevi, and
vascular malformations. Tumors, mostly benign but some malignant, have also
been reported in Proteus syndrome, generally presenting by the age of 20 years
and including papillary adenocarcinoma of the testis, meningioma, and cystadenoma
of the ovaries.
A microdeletion of chromosome 10q23
involving PTEN and BMPR1A is a cause of chromosome 10q23 deletion syndrome.
This syndrome shows overlapping features of the following three disorders:
Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.
References (open access):
Roles of the Raf/MEK/ERK and
PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to
therapy-implications for cancer and aging. Steelman LS, Chappell WH, Abrams SL,
Kempf RC, Long J, Laidler P, Mijatovic S, Maksimovic-Ivanic D, Stivala F,
Mazzarino MC, Donia M, Fagone P, Malaponte G, Nicoletti F, Libra M, Milella M,
Tafuri A, Bonati A, Bäsecke J, Cocco L, Evangelisti C, Martelli AM, Montalto G,
Cervello M, McCubrey JA. Aging (AlbanyNY). 2011 Mar;3(3):192-222.
The PTEN phosphatase controls intestinal
epithelial cell polarity and barrier function: role in colorectal cancer
progression. Langlois MJ, Bergeron S, Bernatchez G, Boudreau F, Saucier C,
Perreault N, Carrier JC, Rivard N. PLoS One. 2010 Dec 23;5(12):e15742.