• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6243-6246
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• 2014

To investigate the role of miR-1297 and the tumor suppressor gene PTEN in cell proliferation of testicular germ cell tumors (TGCT). MTT assays were used to test the effect of miR-1297 on proliferation of the NCCIT testicular germ cell tumor cell line. In NCCIT cells, the expression of PTEN was assessed by Western blotting further. In order to confirm target association between miR-1297 and 3'-UTR of PTEN, a luciferase reporter activity assay was employed. Moreover, roles of PTEN in proliferation of NCCIT cells were evaluated by transfection of PTEN siRNA. Proliferation of NCCIT cells was promoted by miR-1297 in a concentration-dependent manner. In addition, miR-1297 could bind to the 3'-UTR of PTEN based on luciferase reporter activity assay, and reduced expression of PTEN at protein level was found. Proliferation of NCCIT cells was significantly enhanced after knockdown of PTEN by siRNA. miR-1297 as a potential oncogene could induce cell proliferation by targeting PTEN in NCCIT cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.17-24
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• 2014

Gastric cancer is highly invasive, aggressively malignant, and amongst the most prevalent of all forms of cancer. Despite improved management strategies, early stage diagnosis of gastric cancer and accurate prognostic assessment is still lacking. Several recent reports have indicated that the pathogenesis of gastric cancer involves complex molecular mechanisms and multiple genetic and epigenetic alterations in oncogenes and tumor suppressor genes. Functional inactivation of the tumor suppressor protein PTEN (Phosphatase and Tensin Homolog) has been detected in multiple cases of gastric cancer, and already shown to be closely linked to the development, progression and prognosis of the disease. Inactivation of PTEN can be attributed to gene mutation, loss of heterozygosity, promoter hypermethylation, microRNA- mediated regulation of gene expression, and post-translational phosphorylation. PTEN is also involved in mechanisms regulating tumor resistance to chemotherapy. This review provides a comprehensive analysis of PTEN and its roles in gastric cancer, and emphasizes its potential benefits in early diagnosis and gene therapy-based treatment strategies.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.1
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• pp.17-20
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• 2004

PTEN (phosphatase and tensin homolog) is a dual specific phosphatase antagonizing phosphoinositide 3-kinase activity, and has first been cloned as a tumor suppressor for glioma. Although the role of PTEN as a tumor suppressor has been well studied, little is known about signaling mechanisms regulating expression and/or activity of PTEN in the central nervous system. In this study, we investigated whether PTEN expression is regulated by sensory deprivation. P5 rat pups were unilaterally naris-closed, and olfactory bulbs were immunohistochemically analyzed with PTEN antibody at the $7^{th}$ day after naris closure. PTEN immunoreactivity was found to be down-regulated in both glomerular, external plexiform and subependymal cell layers, suggesting that odor deprivation signals down-regulate expression of PTEN in the olfactory bulb. To the best of our knowledge, this is the first report to suggest that PTEN expression is regulated by sensory deprivation signals in neonatal rats.

• Molecules and Cells
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• v.44 no.8
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• pp.613-622
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• 2021

In vertebrate eyes, the retinal pigment epithelium (RPE) provides structural and functional homeostasis to the retina. The RPE takes up retinol (ROL) to be dehydrogenated and isomerized to 11-cis-retinaldehyde (11-cis-RAL), which is a functional photopigment in mammalian photoreceptors. As excessive ROL is toxic, the RPE must also establish mechanisms to protect against ROL toxicity. Here, we found that the levels of retinol dehydrogenases (RDHs) are commonly decreased in phosphatase tensin homolog (Pten)-deficient mouse RPE, which degenerates due to elevated ROL and that can be rescued by feeding a ROL-free diet. We also identified that RDH gene expression is regulated by forkhead box O (FOXO) transcription factors, which are inactivated by hyperactive Akt in the Pten-deficient mouse RPE. Together, our findings suggest that a homeostatic pathway comprising PTEN, FOXO, and RDH can protect the RPE from ROL toxicity.

• BMB Reports
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• v.46 no.10
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• pp.490-494
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• 2013

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor-suppressing lipid phosphatase that is frequently absent in breast tumors. Thus, the stability of PTEN is essential for tumor prevention and therapy. The ubiquitin-proteasome pathway has an important role in regulating the functions of PTEN. Specifically, carboxyl terminus Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase of PTEN, can regulate PTEN levels. In this study, we report that BCL-2-associated athanogene 5 (BAG5), a known inhibitor of CHIP activity, reduces the degradation of PTEN and maintains its levels via an ubiquitylation-dependent pathway. BAG5 is identified as an antagonist of cell tumorigenicity.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.20 no.1
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• pp.65-70
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• 2017

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is one of the phosphatase and tensin homolog hamartoma tumor syndrome with a PTEN gene mutation. It is a rare dominant autosomal disorder characterized by cutaneous lipomas, macrocephaly, intestinal polyps, and developmental delay. Diagnosing this syndrome is important, because it may represent the pediatric phenotype of Cowden syndrome, in which there is an increased risk for malignant tumors in children. Until now, the prevalence of BRRS is unknown. Several dozen cases have been reported in the medical literature, but no case has been reported in Korea. Here we report a case of a 19-year-old girl who was diagnosed with BRRS because of macrocephaly, intellectual disability, and intestinal polyps. Her mother had similar findings and a PTEN mutation. Neither patient had mutations detected by conventional mutation-detection techniques, but a PTEN gene deletion was demonstrated by chromosomal microarray analysis.

• Clinical and Experimental Reproductive Medicine
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• v.39 no.1
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• pp.10-14
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• 2012

The ovarian follicles develop initially from primordial follicles. The majority of ovarian primordial follicles are maintained quiescently as a reserve for the reproductive life span. Only a few of them are activated and develop to an advanced follicular stage. The maintenance of dormancy and activation of primordial follicles are controlled by coordinated actions of a suppressor/activator with close communications with somatic cells and intra-oocyte signaling pathways. Many growth factors and signaling pathways have been identified and the transforming growth factor-beta superfamily plays important roles in early folliculogenesis. However, the mechanism of maintaining the dormancy and survival of primordial follicles has remained unknown for decades. Recently, since the first finding that all primordial follicles are activated prematurely in mice deficient forkhead box O3a, phosphatidylinositol 3 kinase/phosphatase and tensin homolog (PTEN) signaling pathway was reported to be important in the regulation of dormancy and initial follicular activation. With these informations on early folliculogenesis, clinical application can be expected such as in vitro maturation of immature oocytes or in vitro activation of follicles by PTEN inhibitor in cryopreserved ovarian cortical tissues for fertility preservation.

• Journal of Breast Disease
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• v.6 no.2
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• pp.79-83
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• 2018

Cowden syndrome (CS), also known as multiple hamartomas syndrome, is a rare hereditary autosomal dominant disorder caused by a germline mutation in the phosphatase and tensin homolog (PTEN) gene mapped on chromosome 10. The clinical features of CS are variable, primarily presenting as mucocutaneous lesions (99%). A mucocutaneous lesion, such as trichilemmoma of the face or keratosis of the extremities, is an important diagnostic marker for CS. CS has been reported to increase the incidence of benign and malignant neoplasms in the breast, thyroid, and gastrointestinal tract. The risk of developing malignancy in individuals with CS is up to 10 times higher than general population throughout an entire life time.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.473-479
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• 2005

Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4691-4698
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• 2015

Background: The tumor suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. However, available results for the prognostic value of PTEN expression in patients with cancer remain controversial. Therefore, a meta-analysis of published studies investigating this issue was performed. Materials and Methods: A literature search via PubMed and EMBASE databases was conducted. Statistical analysis was performed by using the STATA 12.0 (STATA Corp., College, TX). Data from eligible studies were extracted and included into the meta-analysis using a random effects model. Results: A total of 3,810 patients from 27 studies were included in the meta-analysis, 22 investigating the relationship between PTEN expression and overall survival (OS) using univariate analysis, and nine with multivariate analysis. The pooled hazard ratio (HR) for OS was 1.64 (95% confidence interval (CI): 1.32-2.05) by univariate analysis and 1.56 (95% CI: 1.20-2.03) by multivariate analysis. In addition, eight papers including two disease-free-survival analyses (DFSs), four relapse-free-survival analyses (RFSs), three progression-free-survival analyses (PFSs) and one metastasis-free-survival analysis (MFS) reported the effect of PTEN on survival. The results showed that loss of PTEN expression was significant correlated with poor prognosis, with a combined HR of 1.74 (95% CI: 1.24-2.44). Furthermore, in the stratified analysis by the year of publication, ethnicity, cancer type, method, cut-off value, median follow-up time and neoadjuvant therapy in which the study was conducted, we found that the ethnicity, cancer type, method, median follow-up time and neoadjuvant therapy are associated with prognosis. Conclusions: Our study shows that negative or loss of expression of PTEN is associated with worse prognosis in patients with cancer. However, adequately designed prospective studies need to be performed for confirmation.