PTEN Gene: A Model for Genetic Diseases in Dermatology

Abstract

PTEN gene is considered one of the most mutated tumor suppressor genes in human cancer, and it's likely to become the first one in the near future. Since 1997, its involvement in tumor suppression has smoothly increased, up to the current importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome (PHTS), which include the past-called Cowden, Bannayan-Riley-Ruvalcaba, Proteus, Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting only the first tissues where the involvement has been proven. The negative regulation of cell interactions with the extracellular matrix could be the way PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in human development. A recent model sees PTEN function as a stepwise gradation, which can be impaired not only by heterozygous mutations and homozygous losses, but also by other molecular mechanisms, such as transcriptional regression, epigenetic silencing, regulation by microRNAs, posttranslational modification, and aberrant localization. The involvement of PTEN function in melanoma and multistage skin carcinogenesis, with its implication in cancer treatment, and the role of front office in diagnosing PHTS are the main reasons why the dermatologist should know about PTEN.

The role of microRNAs in skin fibrosis

“…The TGF-beta pathway interacts with miRNA-150 and miRNA-196a in collagen synthesis [20,21] and is also involved in fibroblast proliferation (via miRNA-21 and miRNA-31), differentiation (via miRNA-146a), and EMT (via miRNA-21 and miRNA-200) [31,46,52,71]. Considering the key involvement of TGF-beta signaling in skin fibrotic processes, targeting associated miRNAs may prove invaluable in halting skin fibrosis.…”

“…TGF-beta upregulates miRNA-21 and miRNA-21 in turn regulates the expression of the phosphatase and tensin homolog (PTEN) gene [31]. PTEN is a recognized inhibitor of EMT and is targeted and inhibited by miRNA-21 (Figure 4) [46,52]. By blocking the expression of PTEN, miRNA-21 releases the inhibition on EMT resulting in an increase in the number of fibroblasts derived from epithelial cells [31].…”

Gene in Multiple Cancers

“…[30][31][32][33] Focusing on the genetic defect in CS, the widely mentioned gene is PTEN gene. 34,35 The mutations within PTEN gene can be seen in almost all patients with PTEN. Generally, PTEN is a tumor suppressor gene on 10q23.3 which corresponds to encoding a lipid phosphatase that lies upstream of protein kinase B (Akt).…”

“…Generally, PTEN is a tumor suppressor gene on 10q23.3 which corresponds to encoding a lipid phosphatase that lies upstream of protein kinase B (Akt). 35,36 PTEN negatively regulates cell interactions with the extracellular matrix and the aberration of this normal function can result in carcinogenesis. 35…”

Roles of PTEN (Phosphatase and Tensin Homolog) in Gastric Cancer Development and Progression

“…Additionally, it can restrict cellular differentiation by negatively regulating mitogenactivated protein kinase (MAPK)-mediated signaling (Besson et al, 1999;Ciuffreda et al, 2012). Genetic modification-induced inactivation of PTEN has been detected frequently in different forms of cancers, including glioblastoma multiforme, endometrial carcinoma, skin, prostate and breast cancer (Baig et al, 2011;Romano et al, 2012;Cancer Genome Atlas Research Network et al, 2013;Moon et al, 2013;Patel et al, 2013). Different mechanisms have been implicated in PTEN inactivation in gastric cancer; its decreased expression is closely related to the incidence, progression and prognosis of the disease.…”