scholarly journals An Immunohistochemical Study of the PTEN/AKT Pathway Involvement in Canine and Feline Mammary Tumors

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 365
Author(s):  
Pietro Asproni ◽  
Francesca Millanta ◽  
Lorenzo Ressel ◽  
Fabio Podestà ◽  
Francesca Parisi ◽  
...  
Keyword(s):  
Immunohistochemical Study ◽  
Lymphatic Invasion ◽  
Pten Expression ◽  
Akt Pathway ◽  
Phosphatase And Tensin Homolog ◽  
Mammary Carcinomas ◽  
Tensin Homolog ◽  
Aggressive Tumors ◽  
Aggressive Subtype ◽  
Viral Oncogene Homolog

Phosphatase and tensin homolog deleted on chromosome10 (PTEN), phospho-v-Akt murine thymoma viral oncogene homolog (AKT), and the Rapamycin-Insensitive Companion of mTOR (Rictor) expression was investigated by immunohistochemistry in 10 canine mammary adenomas (CMAs), 40 canine mammary carcinomas (CMCs), and 30 feline mammary carcinomas (FMCs). All the CMAs, 25 of 40 CMCs (63%) and 7 of 30 FMCs (23%), were PTEN-positive. In dogs, no CMAs and 15 of 25 CMCs (37%) expressed phospho-AKT (p-AKT), while 24 of 30 FMCs (82%) were p-AKT-positive. One of 10 CMAs (10%), 24 of 40 CMCs (60%) and 20 of 30 FMCs (67%) were Rictor-positive. In the dog, PTEN expression correlated with less aggressive tumors, absence of lymphatic invasion, and longer survival. P-AKT expression correlated with more aggressive subtype, lymphatic invasion, and poorer survival and Rictor expression with lymphatic invasion. In cats, PTEN correlated with less aggressive carcinomas, absence of lymphatic invasion, and better survival. P-AKT and Rictor expression correlated with poorer survival. PTEN expression was inversely correlated with p-AKT and Rictor in both species, while p-AKT positively correlated with Rictor expression. A strong PTEN/AKT pathway involvement in behavior worsening of CMT and FMTs is demonstrated, providing a rationale for further studies of this pathway in veterinary oncology.

LINC00893 inhibits papillary thyroid cancer by suppressing AKT pathway via stabilizing PTEN

2020 ◽  
pp. 1-10
Author(s):  
Shujing Li ◽  
Yanyan Zhang ◽  
Jian Dong ◽  
Ruihuan Li ◽  
Bo Yu ◽  
...  
Keyword(s):  
Akt Pathway ◽  
Phosphatase And Tensin Homolog ◽  
Fused In Sarcoma ◽  
Tensin Homolog ◽  
Phosphorylated Akt ◽  
Pten Mrna ◽  
Non Coding Rnas ◽  
And Migration ◽  
Fus Protein ◽  
Proliferation And Migration

Long non-coding RNAs (lncRNAs) are important to the occurrence and advancement of human cancers. We found through GEPIA that LINC00893 was lowly expressed in thyroid carcinoma (THCA) tissues, whereas the specific functions of LINC00893 has never been reported in PTC. In the current study, we confirmed that LINC00893 was expressed at a low level in PTC cells. Through gain-of-function assays, we determined that LINC00893 overexpression abrogated proliferation and migration abilities of PTC cells. Through signal transduction reporter array we found that LINC00893 potentially modulated the signals of phosphatase and tensin homolog (PTEN)/AKT pathway. In addition, overexpression of LINC00893 increased the expression of PTEN but reduced the levels of phosphorylated AKT in PTC. Additionally, mechanism assays unveiled that LINC00893 stabilized PTEN mRNA via recruiting Fused in sarcoma (FUS) protein. Finally, rescue assays demonstrated that LINC00893 hampered the proliferation and migration of PTC cells via PTEN/AKT pathway. Together, our study first clarified that LINC00893 functions as a tumor suppressor in PTC by blocking AKT pathway through PTEN upregulation.

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 HES1 opposes a PTEN-dependent check on survival, differentiation, and proliferation of TCRβ-selected mouse thymocytes

Blood ◽  
2012 ◽  
Vol 120 (7) ◽  
pp. 1439-1448 ◽  
Author(s):  
Gladys W. Wong ◽  
Gisele C. Knowles ◽  
Tak W. Mak ◽  
Adolfo A. Ferrando ◽  
Juan Carlos Zúñiga-Pflücker
Keyword(s):  
T Cell ◽  
Notch Signaling ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Akt Pathway ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Developmental Progression ◽  
Differentiation And Proliferation ◽  
Immature Thymocytes

Abstract The developmental progression of immature thymocytes requires cooperative input from several pathways, with Notch signals playing an indispensable role at the T-cell receptor (TCR)–β selection checkpoint. Notch signals affect the activation of the PI3K/Akt pathway, which is required for pTα/TCRβ (pre-TCR)–induced survival, differentiation, and proliferation of developing αβ-lineage thymocytes. However, the molecular players responsible for the interaction between the Notch and PI3K pathways at this critical developmental stage are unknown. Here, we show that Notch induction of Hes1 is necessary to repress the PI3K/Akt pathway inhibitor, PTEN (phosphatase and tensin homolog), which in turn facilitates pre-TCR–induced differentiation. In support of this mechanism, deletion or down-regulation of Pten overcomes the Notch signaling requirement for survival and differentiation during β-selection. In addition, c-Myc is a critical target of Notch at this stage, as c-Myc expression overcomes the Notch signaling requirement for proliferation during β-selection. Collectively, our results point to HES1, via repression of PTEN, and c-Myc as critical mediators of Notch function at the β-selection checkpoint.

scholarly journals The Major Target of the Endogenously Generated Reactive Oxygen Species in Response to Insulin Stimulation Is Phosphatase and Tensin Homolog and Not Phosphoinositide-3 Kinase (PI-3 Kinase) in the PI-3 Kinase/Akt Pathway

2005 ◽  
Vol 16 (1) ◽  
pp. 348-357 ◽  
Author(s):  
Ji Hae Seo ◽  
Younghee Ahn ◽  
Seung-Rock Lee ◽  
Chang Yeol Yeo ◽  
Kyu Chung Hur
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Membrane Fraction ◽  
Akt Pathway ◽  
Oxygen Species ◽  
Insulin Stimulation ◽  
Phosphatase And Tensin Homolog ◽  
Downstream Signaling ◽  
Tensin Homolog ◽  
Phosphoinositide 3 Kinase

Phosphoinositide-3 kinase (PI-3 kinase) and its downstream signaling molecules PDK-1 and Akt were analyzed in SK-N-SH and SK-N-BE(2) human neuroblastoma cell lines. When cells were stimulated with insulin, PI-3 kinase was activated in both cell lines, whereas the translocation of PDK-1 to the membrane fraction and phosphorylated Akt were observed only in SK-N-SH cells. Analyses of the insulin-mediated reactive oxygen species (ROS) generation and Phosphatase and Tensin homolog (PTEN) oxidation indicate that PTEN oxidation occurred in SK-N-SH cells, which can produce ROS, but not in SK-N-BE(2) cells, which cannot increase ROS in response to insulin stimulation. When SK-N-SH cells were pretreated with the NADPH oxidase inhibitor diphenyleneiodonium chloride before insulin stimulation, insulin-mediated translocation of PDK-1 to the membrane fraction and phosphorylation of Akt were remarkably reduced, whereas PI-3 kinase activity was not changed significantly. These results indicate that not only PI-3 kinase activation but also inhibition of PTEN by ROS is needed to increase cellular level of phosphatidylinositol 3,4,5-trisphosphate for recruiting downstream signaling molecules such as PDK-1 and Akt in insulin-mediated signaling. Moreover, the ROS generated by insulin stimulation mainly contributes to the inactivation of PTEN and not to the activation of PI-3 kinase in the PI-3 kinase/Akt pathway.

scholarly journals Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Masanobu Kawai ◽  
Saori Kinoshita ◽  
Keiichi Ozono ◽  
Toshimi Michigami
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Regulatory Network ◽  
Fibroblast Growth Factor 23 ◽  
Pten Expression ◽  
Fibroblast Growth ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Mtorc1 Pathway

AbstractFibroblast growth factor 23 (FGF23) has been centric to the regulation of phosphate (Pi) metabolism; however, the regulatory network of FGF23 in osteocytes has not yet been defined in detail. We herein investigated the role of PTEN (phosphatase and tensin homolog deleted from chromosome 10) in this regulation. We created mice lacking PTEN expression mainly in osteocytes by crossing Pten-flox mice with Dmp1-Cre mice. The lack of PTEN in the osteocytes of these mice was associated with decreased skeletal and serum intact FGF23 levels, which, in turn, resulted in reductions of urinary Pi excretion and elevations of serum Pi levels. Mechanistically, the knockdown of PTEN expression in osteoblastic UMR106 cells activated the AKT/mTORC1 (mechanistic target of rapamycin complex 1) pathway and this was associated with reductions in Fgf23 expression. Furthermore, the suppression of Fgf23 expression by PTEN knockdown or insulin simulation in UMR106 cells was partially restored by the treatment with the mTORC1 inhibitor, rapamycin. These results suggest that FGF23 expression in osteoblastic cells is in part regulated through the AKT/mTORC1 pathway and provide new insights into our understanding of the regulatory network of Pi metabolism.

scholarly journals The Protective Effect of Early Hypothermia on PTEN Phosphorylation Correlates with Free Radical Inhibition in Rat Stroke

2009 ◽  
Vol 29 (9) ◽  
pp. 1589-1600 ◽  
Author(s):  
Sang Mi Lee ◽  
Heng Zhao ◽  
Carolina M Maier ◽  
Gary K Steinberg
Keyword(s):  
Protective Effect ◽  
Artery Occlusion ◽  
Akt Pathway ◽  
Moderate Hypothermia ◽  
Ischemic Damage ◽  
Protective Mechanisms ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Phosphorylated Akt ◽  
Transient Focal Ischemia

We recently showed that intraischemic moderate hypothermia (30°C) reduces ischemic damage through the Akt pathway after permanent distal middle cerebral artery occlusion in rats. The only Akt pathway component preserved by hypothermia is phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (p-PTEN), which suggests that p-PTEN may have a central role in neuroprotection. Reactive oxygen species (ROS) are critically involved in mediating ischemic damage after stroke by interacting with signaling molecules, including Akt, PTEN, and δ-protein kinase C (PKC). We investigated the protective mechanisms of moderate hypothermia on these signaling proteins after transient focal ischemia in rats. Early moderate hypothermia (3h) was administered 15 mins before reperfusion, and delayed moderate hypothermia (3h) was applied 15 mins after reperfusion. Our results indicate that early hypothermia reduced infarction, whereas delayed hypothermia did not. However, both early and delayed hypothermia maintained levels of Mn-SOD (superoxide dismutase) and phosphorylated Akt and blocked δ-PKC cleavage, suggesting that these factors may not be critical to the protection of hypothermia. Nevertheless, early hypothermia preserved p-PTEN levels after reperfusion, whereas delayed hypothermia did not. Furthermore, ROS inhibition maintained levels of p-PTEN after stroke. Together, these findings suggest that phosphorylation levels of PTEN are closely associated with the protective effect of early hypothermia against stroke.

scholarly journals Association between PTEN and clinical-pathological features of osteosarcoma

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Jian Zhou ◽  
Xia Xiao ◽  
Wanchun Wang ◽  
Yingquan Luo
Keyword(s):  
Meta Analysis ◽  
Clinicopathological Features ◽  
Pten Expression ◽  
Cochrane Library ◽  
Medical Database ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Positive Expression ◽  
The Cochrane Library ◽  
The Relationship

Abstract Previous studies indicated the prognostic value of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in osteosarcoma (OS). There was a great degree of inconsistency between these reports. The aim of this meta-analysis was to investigate the clinicopathological features and prognostic role of PTEN positive expression on OS. We searched NCBI PubMed, Embase, Springer, ISI Web of Knowledge, the Cochrane library, China National Knowledge Internet database (CNKI), Wanfang database, Chinese VIP database and Chinese Biological Medical Database (CBM) for relevant papers published before 28 November 2018. The eligibility of all retrieved studies assessing the relationship between PTEN expression and clinicopathological and prognostic outcomes in OS were incorporated. Pooled odds ratio (OR) and 95% confidence intervals (CIs) were used to estimate the outcomes. A total of 13 studies with 580 OS patients were involved to assess the relationship between PTEN expression and clinicopathological features of OS. PTEN positive expression was significantly associated with male (OR = 1.57, 95% CI: 1.03–2.38, P=0.035<0.05) and OS high differentiation (OR = 2.33, 95% CI: 1.26–4.29, P=0.007<0.05). Additionally, positive expressions of PTEN predict no neoplasm metastasis (OR = 5.69, 95% CI: 3.64–8.90, P<0.05). The results of our study showed that positive expression of PTEN may predict higher 5-year survival in OS with the pooled OR of 8.73 (95% CI: 4.18–18.24, P<0.05). The results from the present study suggest that positive expression of PTEN is significantly associated with male, high differentiation, no metastasis and high 5-year overall survival rate in OS.

The mitogen-activated protein kinase (MAPK) cascade controls phosphatase and tensin homolog (PTEN) expression through multiple mechanisms

2012 ◽  
Vol 90 (6) ◽  
pp. 667-679 ◽  
Author(s):  
Ludovica Ciuffreda ◽  
Cristina Di Sanza ◽  
Ursula Cesta Incani ◽  
Adriana Eramo ◽  
Marianna Desideri ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mapk Cascade ◽  
Pten Expression ◽  
Mitogen Activated Protein Kinase ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Mitogen Activated Protein
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