• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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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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• 제15권1호
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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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• 제8권1호
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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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• 제44권8호
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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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• 제46권10호
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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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• 제20권1호
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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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• 제39권1호
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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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• 제6권2호
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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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• 제58권5호
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• pp.473-479
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• 2005

연구 배경 : Gefitinib은 경구용 상피세포 성장인자 수용체 억제제로서 주로 동양인, 여성, 비흡연가, 선암 세포형의 폐암 환자에서 반응율이 좋은 것으로 되어 있으나 그 정확한 기전에 대해 밝혀진 것을 없다. 최근 몇몇 보고에 의하면 병기가 진행된 폐암 세포에서 PTEN 발현이 감소되어 있었으며, 또한 PTEN 발현이 감소된 폐암 세포주에서 EGFR tyrosine kinase inhibitor의 반응율이 감소되었음을 보고한 논문들이 있다. 이에 저자들은 본원에서 비소세포 폐암으로 진단받고 표준 항암화학요법에 실패한 이후 gefitinib으로 치료받은 환자군의 폐조직을 대상으로 PTEN의 발현 정도를 조사하였으며, PTEN의 발현 정도와 임상병기, 치료반응율과의 상관관계에 대해 분석하였다. 대상 및 방법 : 2002년 1월부터 2004년 8월까지 본원에 내원하여 원발성 비소세포성 폐암 진단 받은 후 표준 항암 화학요법에 실패하고 gefitinib을 복용한 환자 38명 중 2개월 이상을 투여 받아 반응 정도를 평가가 가능한 환자로서 폐조직에 대해 PTEN 면역조직화학 염색 및 정량화를 시행할 수 있었던 22명의 환자들에 대해 환자들의 약제 반응율과 PTEN의 발현양상과의 관계에 대해 후향적으로 조사하였다. 결 과 : 평균 연령은 62세, 남녀의 비는 6.3:1이었으며, 조직 병리학적 분류는 편평상피암 32%, 선암 59%, 대세포암 등 기타가 9%였다. 병기는 I 병기 1례, II 병기 1례, III 병기 9례, IV 병기가 11례였다. ECOG performance status는 grade 0-1이 9명, 2가 11명, 3이 2명이었다. 조직 병리학적 분류에 따른 PTEN 발현의 유의한 차이는 없었다. 또한 TNM 병기 상승에 따른 PTEN 발현율과는 서로 통계적으로 유의한 차이가 없었다. 그 러나, 약제 반응을 보인 군에서 약제 반응을 보이지 않은 군보다 PTEN 발현율이 통계적으로 유의하게 높게 나타났다(p=0.039). 결 론 : 표준 항암 화학 요법에 실패하고 gefitinib을 복용한 비소세포 폐암 환자의 약제 반응율과 종양 억제 단백질인 PTEN의 발현율과 서로 상관관계가 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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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.