Disease relevance of TNS1

• This observation was explained by the elevated expression of the phosphatase and tensin homologue (PTEN), a recently characterized tumour suppressor, in papilloma tissue [1].
• AIM: To investigate the tumor-suppressive effect of the phosphatase and tensin homologue deleted from chromosome (PTEN) in human gastric cancer cells that were wild type for PTEN [2].
• The effects and mechanisms of exogenous phosphatase and tensin homolog deleted from chromosome ten (PTEN) gene on phosphatase activity-dependent apoptosis of breast cancer cell line MDA468 were investigated [3].
• Pten (phosphatase and tensin homologue gene) haploinsufficiency promotes insulin hypersensitivity [4].
• In mice, widespread deletion of the tumor suppressor Phosphatase and tensin homolog (PTEN) generates hamartomatous intestinal polyps with epithelial and stromal involvement [5].

Psychiatry related information on TNS1

• Mutations of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a protein and lipid phosphatase, have been associated with gliomas, macrocephaly, and mental deficiencies [6].
• Polymorphisms in the phosphate and tensin homolog gene are not associated with late-onset Alzheimer's disease [7].
• The efficacy of the TNS was investigated in two placebo-controlled double-blind smoking cessation programs with minimal contact and minimal psychological support [8].

High impact information on TNS1

• However, mutations in MADH4 are only present in a subset of JP cases, and although mutations in the gene for phosphatase and tensin homolog (PTEN) have been described in a few families, undefined genetic heterogeneity remains [9].
• Proteins that bind to the barbed end, including capping protein, the gelsolin super-family, tensin, and profilin are discussed, as are proteins that bind to the pointed end, including tropomodulin and spectrin/band 4 [10].
• PTEN (phosphatase and tensin homologue) is a phosphatase that dephosphorylates both protein and phosphoinositide substrates [11].
• Fibrillar adhesions arise from the medial ends of stationary focal contacts, contain alpha5beta1 integrin and tensin but not other focal-contact components, and associate with fibronectin fibrils [12].
• Here we use time-lapse microscopy to analyse cell-matrix adhesions in cells expressing one of two different cytoskeletal proteins, paxillin or tensin, tagged with green fluorescent protein (GFP) [12].

Chemical compound and disease context of TNS1

• Phosphatase protein homologue to tensin expression and phosphatidylinositol-3 phosphate kinase mutations in colorectal cancer [13].
• Fifty-six patients with angina pectoris on effort participated in a 28-day study comparing a transdermal nitroglycerin system (TNS) against placebo [14].
• This study shows the signaling pathway by which cilostazol suppresses tumor necrosis factor-alpha (TNF-alpha)-induced the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) phosphorylation and apoptosis via casein kinase 2 (CK2) phosphorylation in the SK-N-SH cells (neuroblastoma cells) [15].
• The transdermal administration of nicotine by means of a transdermal nicotine system (TNS) affords a novel way of nicotine replacement to alleviate smoking cessation [8].
• Here, we report that rosiglitazone reduced the phosphorylation of Akt and increased phosphatase and tensin homologue (PTEN) protein expression in non-small cell lung carcinoma (NSCLC) cells (H1792 and H1838), and this was associated with inhibition of NSCLC cell proliferation [16].

Biological context of TNS1

• Nephrocystin is an adaptor protein that is able to associate with signaling molecules involved in cell adhesion and actin cytoskeleton organization, such as p130Cas, Pyk2, tensin and filamins [17].
• Phosphatase and tensin homolog (PTEN), deleted on chromosome 10, is a potent tumor suppressor [18].
• BACKGROUND & AIMS: PTEN (phosphatase and tensin homologue deleted from chromosome 10) is a dual-specificity phosphatase implicated in embryonic development, intestinal cell proliferation and differentiation, and tumor suppression [19].
• PTEN is a novel tumour suppressor gene that encodes a dual-specificity phosphatase with homology to adhesion molecules tensin and auxillin [20].
• Both wortmannin and transient overexpression of the dual lipid/protein phosphatase and tensin homolog deleted on chromosome 10 enhanced doxorubicin-induced cell death [21].

Anatomical context of TNS1

• The leukemic T cell line Jurkat is deficient in protein expression of the lipid phosphatases Src homology 2 domain containing inositol polyphosphate phosphatase (SHIP) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) [22].
• Finally, tensin is rapidly cleaved by a focal-adhesion protease, calpain II [23].
• Tensin is a focal-adhesion molecule that binds to actin filaments and interacts with phosphotyrosine-containing proteins [23].
• In normal kidney, immunohistochemistry revealed that tensin was localized in MCs and parietal epithelial cells as well as TECs [24].
• In human mesangial cells (MCs) and TECs, we confirmed mRNA and protein expressions of tensin by RT-PCR and immunoprecipitation [24].

Associations of TNS1 with chemical compounds

• The PTEN (phosphatase and tensin homologue deleted on chromosome 10) tumor suppressor is a phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) 3-phosphatase that plays a crucial role in regulating many cellular processes by antagonizing the phosphoinositide 3-kinase signaling pathway [25].
• Shikonin inhibited the phosphatidylinositol 3,4,5-triphosphate (PtdIns-3,4,5-P3) phosphatase activity of recombinant phosphatase and tensin homolog deleted on chromosome 10 (PTEN) with an IC50 value of 2.7 microM [26].
• A naphthoquinone derivative, shikonin, has insulin-like actions by inhibiting both phosphatase and tensin homolog deleted on chromosome 10 and tyrosine phosphatases [26].
• The tumour suppressor protein, PTEN (phosphatase and tensin homolog deleted on chromosome 10), is a phosphatase that can dephosphorylate tyrosine-containing peptides, Shc, focal adhesion kinase and phosphoinositide substrates [27].
• Integrin alpha5, but not alpha1 and alpha3, colocalized with tensin [24].
• Point mutation of a critical tyrosine residue (Y442F) in DLC1 rendered the protein deficient for binding the tensin SH2 domain and binding full-length tensin [28].

Physical interactions of TNS1

• Human cten cDNA encodes a 715 amino acid sequence containing the Src homology 2 and phosphotyrosine-binding domains that are similar to the COOH termini of tensin molecules [29].
• Tensin binds to actin filaments at the focal adhesion contacts and it links the actin cytoskeleton to the extracellular matrix (ECM) [30].

Enzymatic interactions of TNS1

• In addition, mutations in the phosphatase and tensin homolog deleted on chromosome ten (PTEN), one of the most frequently mutated tumor suppressor genes, results in elevated PKB activity [31].
• NGF/p75NTR-activated CK2 phosphorylates the phosphatase and tensin homologue deleted on chromosome 10 (PTEN), thus rendering this phosphatase inactive [32].

Regulatory relationships of TNS1

• Integrin dynamics and matrix assembly: tensin-dependent translocation of alpha(5)beta(1) integrins promotes early fibronectin fibrillogenesis [33].
• Cilostazol enhances casein kinase 2 phosphorylation and suppresses tumor necrosis factor-alpha-induced increased phosphatase and tensin homolog deleted from chromosome 10 phosphorylation and apoptotic cell death in SK-N-SH cells [15].

Other interactions of TNS1

• Class I(A) (PI3Kalpha, beta and delta) and class I(B) (PI3Kgamma) PI3Ks mediate distinct phenotypes in the heart and under negative control by the 3'-lipid phosphatase, phosphatase and tensin homolog on chromosome ten (PTEN) which dephosphorylate PtdIns(3,4,5)P(3) into PtdIns(4,5)P(2) [34].
• We tested whether tensin, a cytoskeletal component localized to both focal contacts and fibronectin-associated fibrillar adhesions, can induce these signaling pathways [35].
• Furthermore, PPARgamma agonists induced expression of protein tyrosine phosphatase-PEST (PTP-PEST), and of phosphatase and tensin homologue deleted on chromosome ten (PTEN) [36].
• An important regulatory mechanism of translational repression under hypoxic conditions involves inhibition of the mammalian target of rapamycin (mTOR). mTOR is a target of the phosphatase and tensin homologue detected on chromosome 10 (PTEN)/phosphatidylinositol 3-kinase/AKT/TSC2 pathway, a pathway that is frequently mutated in human cancers [37].
• Gastrin-releasing peptide-induced down-regulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten) in neuroblastomas [38].

Analytical, diagnostic and therapeutic context of TNS1

• In contrast to other tensin members, cten expression is restricted to prostate and placenta by Northern blot analysis [29].
• TUNEL staining was used to analyze the cytotoxicity of TNFalpha treatment or TNFalpha combined with either the Akt activity inhibitor wortmannin, an adenovirus expressing dominant-negative mutant (AdAkt-DN), or an adenovirus expressing phosphatase and tensin homolog deleted on chromosome 10 (AdPTEN) [39].
• Other tumour suppressor genes, such as retinoblastoma (Rb) and PTEN (phosphatase, tensin homologue, deleted on chromosome 10), are the targets for imminent clinical trials, while microarray technologies are revealing multiple new genes that are potential targets for future gene therapy [40].
• In normal lung fibroblasts but not in fibrotic lung fibroblasts, we show that ligation of alpha4beta1 integrin induces a significant increase in phosphatase and tensin homologue deleted on chromosome 10 (PTEN) activity [41].
• The effects of low frequency (2 Hz) high intensity (10-12 mA) (electroacupuncture, EA) and of high frequency (100 Hz) low intensity (2 mA) (transcutaneous nerve stimulation, TNS) conditioning stimuli were studied on the nociceptive component (R2) of the blink reflex in normal volunteers [42].

References