Tensin Homologue (tensin + homologue)

Distribution by Scientific Domains

Selected Abstracts

Epigenetic and genetic alterations of PTEN in hepatocellular carcinoma

Li Wang
Aim:, To investigate the roles of epigenetic and genetic alterations of the phosphatase and tensin homologue on chromosome 10 gene (PTEN) in carcinogenesis and the development of hepatocellular carcinomas (HCC). Methods:, A total of 56 cases of HCC tissues and six liver cell lines were studied for the expression of PTEN by immunohistochemistry and Western blot analysis. The PTEN gene mutations in exon5 and exon8 were detected by a combination of single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Methylation-specific PCR (MSP) was used to identify PTEN promoter methylation. Results:, Of the 56 cases of HCC, 24 (42.9%) expressed the PTEN protein. All surrounding liver tissues of the hepatoma (32 cases) were positive for PTEN. Of the six cell lines, three liver cancer cell lines showed a low expression of PTEN. Five mutations of 56 HCC samples were detected. All of them were located at intron4. No mutation was found in exon5 and exon8. After MSP analysis, we found nine cases of PTEN promoter methylation in 56 specimens (16.1%). However, no CpG island of PTEN was found to be methylated in all six liver cell lines. Conclusion:, The level of PTEN protein was altered in part of the HCC. The downregulation of PTEN expression may not be mainly associated with the PTEN mutations, but partly due to PTEN promoter methylation and other epigenetic regulation. [source]

Characterization of Phosphatase and Tensin Homolog expression in the mosquito Aedes aegypti: Six splice variants with developmental and tissue specificity

Michael A. Riehle
Abstract Phosphatase and tensin homologue (PTEN), an inhibitor of insulin signalling, was characterized in Aedes aegypti. Surprisingly, six splice variants were identified: three with alternative terminal exons (AaegPTEN2 : 3 : 6) and three formed by intron retention (AaegPTEN1 : 4 : 5). All variants encoded active phosphatase domains. Variants with alternative terminal exons also encoded C2 and COOH-domains, and AaegPTEN6 encoded a PDZ binding motif. These three variants also had unique expression patterns. AaegPTEN2 was expressed primarily in the ovary. AaegPTEN3 was predominant in heads and midguts, and throughout development, except early embryogenesis. AaegPTEN6 was expressed in fat body, ovaries, and throughout development. Intron retention variants were weakly expressed in most samples. These expression patterns suggest that AaegPTEN variants play unique roles in regulating insulin's pleiotropic effects. [source]

Phosphoinositide 3-kinase is not overexpressed in melanocytic lesions

Rajendra S. Singh
Background:, Although various studies have stressed the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-PI3K-AKT pathway in the progression of melanocytic lesions, little is known about the expression pattern of PI3K in these lesions. Objective:, To investigate the expression pattern of PI3K in benign and dysplastic nevi, primary melanomas, and metastatic melanomas and the role of PTEN and PI3K in melanocytic tumor progression. Methods:, Tissue microarrays were constructed using formalin-fixed, paraffin-embedded archival tissue blocks from 89 melanocytic lesions: 17 benign nevi, 18 dysplastic nevi, 23 primary melanomas, and 31 metastatic melanomas. Expression of PTEN and PI3K (p85 and p110 subunits) was evaluated immunohistochemically, and the number of cells and labeling intensity were assessed semiquantitatively. Results:, Both benign and dysplastic nevi showed strong cytoplasmic staining with PTEN, which was subsequently less in melanomas and completely lost in the metastatic lesions. Eleven of 17 (64%) benign nevi, seven of 10 (70%) dysplastic nevi, four of 23 (17%) primaries, and one of 31 (3%) visceral or lymph node metastasis showed strong positivity. Loss of PTEN expression from benign and dysplastic nevi to melanoma was statistically significant (p = 0.001). Although few cells showed reactivity for phosphoinositide 3-kinase (PI3 kinase)-p85 subunit, strong positivity was not detected in the cytoplasm of benign, malignant, or metastatic lesions, except for a single visceral metastasis. Three of 13 (23%) nevi showed positivity for the p110 subunit. No positivity was observed in the dysplastic nevi. Two of 22 (9%) melanomas, one of 14 (7%) visceral metastasis, and three of 12 (25%) lymph node metastasis showed strong positivity. There was no statistical difference in PI3 kinase expression in benign and malignant melanocytic lesions (p = 0.2). Conclusion:, PI3K is not overexpressed in melanocytic lesions. [source]

A mutant form of PTEN linked to autism

PROTEIN SCIENCE, Issue 10 2010
Roberta E. Redfern
Abstract The tumor suppressor, phosphatase, and tensin homologue deleted on chromosome 10 (PTEN), is a phosphoinositide (PI) phosphatase specific for the 3-position of the inositol ring. PTEN has been implicated in autism for a subset of patients with macrocephaly. Various studies identified patients in this subclass with one normal and one mutated PTEN gene. We characterize the binding, structural properties, activity, and subcellular localization of one of these autism-related mutants, H93R PTEN. Even though this mutation is located at the phosphatase active site, we find that it affects the functions of neighboring domains. H93R PTEN binding to phosphatidylserine-bearing model membranes is 5.6-fold enhanced in comparison to wild-type PTEN. In contrast, we find that binding to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) model membranes is 2.5-fold decreased for the mutant PTEN in comparison to wild-type PTEN. The structural change previously found for wild-type PTEN upon interaction with PI(4,5)P2, is absent for H93R PTEN. Consistent with the increased binding to phosphatidylserine, we find enhanced plasma membrane association of PTEN-GFP in U87MG cells. However, this enhanced plasma membrane association does not translate into increased PI(3,4,5)P3 turnover, since in vivo studies show a reduced activity of the H93R PTEN-GFP mutant. Because the interaction of PI(4,5)P2 with PTEN's N-terminal domain is diminished by this mutation, we hypothesize that the interaction of PTEN's N-terminal domain with the phosphatase domain is impacted by the H93R mutation, preventing PI(4,5)P2 from inducing the conformational change that activates phosphatase activity. [source]

PTEN: a promising pharmacological target to enhance epithelial wound healing

M Zhao
PI3Ks (phosphoinositide-3 kinases) produce PIP3 (phosphatidylinositol(3,4,5)-trisphosphate) which mediates signals for cell survival and proliferation. The tumour suppressor PTEN (phosphatase and tensin homologue) dephosphorylates PIP3 and is a key negative regulator of PI3K signalling. Recent research highlighted important roles for PI3K/PTEN in cell polarization and directional cell migration, pointing to a significant role for PTEN in wound healing where spatially organized tissue growth is essential. Lai et al. (in this issue of British Journal of Pharmacology) have moved a step closer in utilizing PTEN for wound healing through pharmacological inhibition. Two vanadium derivative inhibitors targeting PTEN significantly elevated the level of phosphorylated Akt (protein kinase B) and nearly doubled the wound healing rate in monolayer cultures of lung and airway epithelial cells. Damage to airway and lung epithelia underlies a wide spectrum of significant clinical conditions. With further experiments, this promising approach may find potential clinical use in situations where enhanced wound healing of pulmonary and other epithelia is important. British Journal of Pharmacology (2007) 152, 1141,1144; doi:10.1038/sj.bjp.0707503; published online 8 October 2007 [source]