scholarly journals Induction of Apoptotic Genes by a p73-Phosphatase and Tensin Homolog (p73-PTEN) Protein Complex in Response to Genotoxic Stress

2011 ◽  
Vol 286 (42) ◽  
pp. 36631-36640 ◽  
Author(s):  
Jason A. Lehman ◽  
David L. Waning ◽  
Christopher N. Batuello ◽  
Rocky Cipriano ◽  
Madhavi P. Kadakia ◽  
...  
Keyword(s):  
Protein Complex ◽  
Genotoxic Stress ◽  
Pten Protein ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Apoptotic Genes

In silico approach of naringin as potent phosphatase and tensin homolog (PTEN) protein agonist against prostate cancer

2020 ◽  
pp. 1-10 ◽  
Author(s):  
Sankar Muthumanickam ◽  
Thangamariyappan Indhumathi ◽  
Pandi Boomi ◽  
Ramachandran Balajee ◽  
Jeyaraman Jeyakanthan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
In Silico ◽  
Pten Protein ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

Reduced PTEN Protein Expression and Its Prognostic Implications in Canine and Feline Mammary Tumors

2009 ◽  
Vol 46 (5) ◽  
pp. 860-868 ◽  
Author(s):  
L. Ressel ◽  
F. Millanta ◽  
E. Caleri ◽  
V. M. Innocenti ◽  
A. Poli
Keyword(s):  
Protein Expression ◽  
Lymphatic Vessel ◽  
Mammary Tumors ◽  
Lymphatic Vessel Invasion ◽  
Pten Protein ◽  
Phosphatase And Tensin Homolog ◽  
Mammary Carcinomas ◽  
Tensin Homolog ◽  
Vessel Invasion ◽  
Distant Organ

Phosphatase and tensin homolog (PTEN) belongs to the group of gatekeeper tumor suppressor genes and is involved in multiple mechanisms leading to cellular defense against neoplastic transformation and progression. Twenty-four dogs and 17 cats were submitted to a 2-year follow-up study, and clinicopathologic features were recorded and compared with immunohistochemical PTEN staining. PTEN-negative status occurred in 33% of canine and 76% of feline mammary carcinomas. In canine mammary carcinomas, there was a significant ( P < .05) correlation between loss of PTEN protein expression and simple carcinoma histotype, lymphatic vessel invasion, lymph node metastases, distant organ metastases, tumor dedifferentiation, tumor recurrence, and shorter overall survival. In feline mammary tumors, a significant correlation between loss of PTEN protein expression and lymphatic vessel invasion was found. Loss of PTEN expression could be a useful prognostic marker in canine mammary carcinomas.

scholarly journals Molecular Analysis of AFP and HSA Interactions with PTEN Protein

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Mingyue Zhu ◽  
Bo Lin ◽  
Peng Zhou ◽  
Mengsen Li
Keyword(s):  
Molecular Docking ◽  
Molecular Mechanisms ◽  
Docking Study ◽  
Phosphatidylinositol 3 Kinase ◽  
Molecular Docking Study ◽  
Pten Protein ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Significant Homology ◽  
Modeling Data

Human cytoplasmic alpha-fetoprotein (AFP) has been classified as a member of the albuminoid gene family. The protein sequence of AFP has significant homology to that of human serum albumin (HSA), but its biological characteristics are vastly different from HSA. The AFP functions as a regulator in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway, but HSA plays a key role as a transport protein. To probe their molecular mechanisms, we have applied colocalization, coimmunoprecipitation (co-IP), and molecular docking approaches to analyze the differences between AFP and HSA. The data from colocalization and co-IP displayed a strong interaction between AFP and PTEN (phosphatase and tensin homolog), demonstrating that AFP did bind to PTEN, but HSA did not. The molecular docking study further showed that the AFP domains I and III could contact with PTEN.In siliconsubstitutions of AFP binding site residues at position 490M/K and 105L/R corresponding to residues K490 and R105 in HSA resulted in steric clashes with PTEN residues R150 and K46, respectively. These steric clashes may explain the reason why HSA cannot bind to PTEN. Ultimately, the experimental results and the molecular modeling data from the interactions of AFP and HSA with PTEN will help us to identify targets for designing drugs and vaccines against human hepatocellular carcinoma.

scholarly journals Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor

2021 ◽  
Vol 12 ◽  
Author(s):  
Tianyu He ◽  
Xiaoyun Zhang ◽  
Jianyu Hao ◽  
Shigang Ding
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Malignant Tumors ◽  
Biological Effects ◽  
Pten Protein ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Lipid Phosphatase ◽  
And Migration

The Phosphatase and tensin homolog (PTEN) gene is one of the most important tumor suppressor genes, which acts through its unique protein phosphatase and lipid phosphatase activity. PTEN protein is widely distributed and exhibits complex biological functions and regulatory modes. It is involved in the regulation of cell morphology, proliferation, differentiation, adhesion, and migration through a variety of signaling pathways. The role of PTEN in malignant tumors of the digestive system is well documented. Recent studies have indicated that PTEN may be closely related to many other benign processes in digestive organs. Emerging evidence suggests that PTEN is a potential therapeutic target in the context of several non-neoplastic diseases of the digestive tract. The recent discovery of PTEN isoforms is expected to help unravel more biological effects of PTEN in non-neoplastic digestive diseases.

scholarly journals A saturation mutagenesis approach to understanding PTEN lipid phosphatase activity and genotype-phenotypes relationships

2018 ◽  
Author(s):  
Taylor L. Mighell ◽  
Sara Evans-Dutson ◽  
Brian j. O’Roak
Keyword(s):  
Phosphatase Activity ◽  
Autism Spectrum ◽  
Saturation Mutagenesis ◽  
Single Amino Acid ◽  
Pten Protein ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Lipid Phosphatase ◽  
Functional Scores

ABSTRACTPhosphatase and tensin homolog (PTEN) is a tumor suppressor frequently mutated in diverse cancers. Germline PTEN mutations are also associated with a range of clinical outcomes, including PTEN hamartoma tumor syndrome (PHTS) and autism spectrum disorder (ASD). To empower new insights into PTEN function and clinically relevant genotype-phenotype relationships, we systematically evaluated the effect of PTEN mutations on lipid phosphatase activity in vivo. Using a massively parallel approach that leverages an artificial humanized yeast model, we derived high-confidence estimates of functional impact for 7,244 single amino acid PTEN variants (86% of possible). These data uncovered novel insights into PTEN protein structure, biochemistry, and mutation tolerance. Variant functional scores can reliably discriminate likely pathogenic from benign alleles. Further, 32% of ClinVar unclassified missense variants are phosphatase deficient in our assay, supporting their reclassification. ASD associated mutations generally had less severe fitness scores relative to PHTS associated mutations (p = 7.16×10-5) and a higher fraction of hypomorphic mutations, arguing for continued genotype-phenotype studies in larger clinical datasets that can further leverage these rich functional data.

scholarly journals Different Conformations of Phosphatase and Tensin Homolog, Deleted on Chromosome 10 (PTEN) Protein within the Nucleus and Cytoplasm of Neurons

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18857 ◽  
Author(s):  
Vera L. Moncalero ◽  
Roxana V. Costanzo ◽  
Claudia Perandones ◽  
Martin Radrizzani
Keyword(s):  
Chromosome 10 ◽  
Pten Protein ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

scholarly journals Control of Phosphatase and Tensin Homolog (PTEN) Gene Expression in Normal and Neoplastic Thyroid Cells

Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4660-4666 ◽  
Author(s):  
Gianluca Tell ◽  
Alex Pines ◽  
Franco Arturi ◽  
Laura Cesaratto ◽  
Eileen Adamson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Transformation ◽  
Thyroid Tumor ◽  
Pten Gene ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Pten Protein ◽  
Phosphatase And Tensin Homolog ◽  
Protein Levels ◽  
Tensin Homolog

Abstract The lipid phosphatase, phosphatase and tensin homolog (PTEN), is a key element in controlling cell growth and survival and has a well established role as tumor suppressor protein in many neoplasia. Several data indicate that silencing of PTEN gene expression may be relevant in follicular thyroid cell transformation. Thus, in the present study regulation of PTEN gene expression in thyroid cells was investigated. Cotransfection experiments indicated that in normal FRTL-5 rat thyroid cells, PTEN promoter activity was increased by overexpression of the transcription factor early growth response protein-1 (Egr-1). Moreover, Western blot experiments indicated that when Egr-1 expression was up-regulated by treating FRTL-5 cells with H2O2, an increase in PTEN expression was also observed. TSH induced opposite modifications on PTEN and Egr-1 protein levels. Moreover, acute or chronic TSH stimulation determined distinct effects. In fact, acute TSH stimulation (30 and 60 min) induced a decrease in PTEN, but an increase in Egr-1 protein levels. These effects were cAMP dependent; in fact, they were mimicked by forskolin. A chronic TSH treatment (5 d) stimulated PTEN protein expression, whereas Egr-1 protein was down-regulated. In contrast to normal thyroid cells, when the thyroid tumor cell lines ARO and BCPAP were exposed to H2O2, neither Egr-1 nor PTEN protein levels were increased. Acute stimulation of ARO and BCPAP cells with forskolin increased Egr-1, but not PTEN, protein levels. Therefore, thyroid tumor cell lines show alteration of PTEN gene expression regulation. RT-PCR experiments performed on human thyroid tumors showed that the absence of Egr-1 mRNA is always paralleled by the absence of PTEN mRNA. Thus, modification of the Egr-1-dependent mechanisms may play a role in the silencing of PTEN gene expression occurring during thyroid cell transformation.

scholarly journals High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN (Phosphatase and Tensin Homolog)

2020 ◽  
Vol 40 (8) ◽  
pp. 1854-1869
Author(s):  
Keith A. Strand ◽  
Sizhao Lu ◽  
Marie F. Mutryn ◽  
Linfeng Li ◽  
Qiong Zhou ◽  
...  
Keyword(s):  
Protein Expression ◽  
High Throughput ◽  
Knockout Mice ◽  
Vascular Remodeling ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Protective Effects ◽  
High Throughput Screen ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

Objective: Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific PTEN deletion promotes spontaneous vascular remodeling and PTEN loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, PTEN overexpression reduces plaque area and preserves SMC contractile protein expression in atherosclerosis and blunts Ang II (angiotensin II)-induced pathological vascular remodeling, suggesting that pharmacological PTEN upregulation could be a novel therapeutic approach to treat vascular disease. Approach and Results: To identify novel PTEN activators, we conducted a high-throughput screen using a fluorescence based PTEN promoter-reporter assay. After screening ≈3400 compounds, 11 hit compounds were chosen based on level of activity and mechanism of action. Following in vitro confirmation, we focused on 5-azacytidine, a DNMT1 (DNA methyltransferase-1) inhibitor, for further analysis. In addition to PTEN upregulation, 5-azacytidine treatment increased expression of genes associated with a differentiated SMC phenotype. 5-Azacytidine treatment also maintained contractile gene expression and reduced inflammatory cytokine expression after PDGF (platelet-derived growth factor) stimulation, suggesting 5-azacytidine blocks PDGF-induced SMC de-differentiation. However, these protective effects were lost in PTEN-deficient SMCs. These findings were confirmed in vivo using carotid ligation in SMC-specific PTEN knockout mice treated with 5-azacytidine. In wild type controls, 5-azacytidine reduced neointimal formation and inflammation while maintaining contractile protein expression. In contrast, 5-azacytidine was ineffective in PTEN knockout mice, indicating that the protective effects of 5-azacytidine are mediated through SMC PTEN upregulation. Conclusions: Our data indicates 5-azacytidine upregulates PTEN expression in SMCs, promoting maintenance of SMC differentiation and reducing pathological vascular remodeling in a PTEN-dependent manner.

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