Phosphatase and tensin homolog (PTEN) is down-regulated in human NK/T-cell lymphoma and corrects with clinical outcomes

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Nasal-type natural killer/T-cell (NK/T-cell) lymphoma is a more aggressive sub-group of non-Hodgkin lymphoma, which is more common in Asia. The phosphatase and tensin homolog ( PTEN) was originally discovered as a candidate tumor suppressor mutated and lost in various cancers. However, its clinical value and role in NK/T-cell lymphoma remain to be further explored. In the present study, we analyzed PTEN protein expression in 60 cases of human NK/T-cell lymphoma tissues and 40 cases of control nasal mucosa tissues specimens by immunohistochemical analysis. As a result, positive rate of PTEN protein expression in NK/T-cell lymphoma tissues (33.3%) is significantly lower than that of control nasal mucosa tissues (85.0%) ( P < .01). However, no significant association was found between PTEN protein expression and sex, age, tumor location, clinical staging (Ann Arbor staging), or serum lactate dehydrogenase level ( P > .05). Instead, PTEN protein was inversely corrected with Ki-67 expression, indicating a functional role in PTEN in human NK/T-cell lymphoma ( P < .05). For clinical outcomes, PTEN positive rate significantly increased in objective response group (CR+PR) (43.5%) compared with SD+PD group (18.9%). Furthermore, overexpression of PTEN contributed to chemotherapy sensitivity to different doses of cisplatin (DDP) in human NK/T-cell lymphoma SNK-6 cells. These results suggest that PTEN may regulate chemotherapy sensitivity of NK/T-cell lymphoma and contribute to clinical outcomes. These findings indicate PTEN to be a potential target anti-tumor therapeutics for NK/T-cell lymphoma.

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Targeting nonclassical oncogenes for therapy in T-ALL.

Prem S. Subramaniam, Dosh W. Whye, Evgeni Efimenko … (2012)

Constitutive phosphoinositide 3-kinase (PI3K)/Akt activation is common in T cell acute lymphoblastic leukemia (T-ALL). Although four distinct class I PI3K isoforms (α, β, γ, δ) could participate in T-ALL pathogenesis, none has been implicated in this process. We report that in the absence of PTEN phosphatase tumor suppressor function, PI3Kγ or PI3Kδ alone can support leukemogenesis, whereas inactivation of both isoforms suppressed tumor formation. The reliance of PTEN null T-ALL on the combined activities of PI3Kγ/δ was further demonstrated by the ability of a dual inhibitor to reduce disease burden and prolong survival in mice as well as prevent proliferation and promote activation of proapoptotic pathways in human tumors. These results support combined inhibition of PI3Kγ/δ as therapy for T-ALL. Copyright © 2012 Elsevier Inc. All rights reserved.

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PI3K/AKT/PTEN pathway as a target for Crohn's disease therapy (Review).

Nana Tokuhira, Yasuko Kitagishi, Miho M Suzuki … (2015)

The pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease, is a subject of increasing interest. Loss-of-function mutations in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) are strong genetic factors linked to Crohn's disease, which eventually leads to an excessive mucosal inflammatory response directed against components of normal gut microbiota. Reactive oxygen species (ROS) play an important role in inflammation processes, as well as in transduction of signals from receptors for several cytokines, such as tumor necrosis factor α (TNFα). ROS activate nuclear factor-κB (NF-κB) via IκB kinase (IKK) through the PI3K/AKT/PTEN pathway. Therefore, this pathway is recognized to play a key role in Crohn's disease. Loss of function has been demonstrated to occur as an early event in a wide variety of diseases. Given this prevalent involvement in a number of diseases, the molecular development that modulates this pathway has been the subject of several studies. In addition, it has been the focus of extensive research and drug discovery activities. A better understanding of the molecular assemblies may reveal novel targets for the therapeutic development against Crohn's disease.

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PTEN modulators: a patent review.

Chandra Boosani, Devendra K. Agrawal (2013)

PTEN (phosphatase and tensin homolog deleted on chromosome 10) plays a pivotal role in controlling intracellular signaling for cell survival and proliferation by inhibiting the PI3K/Akt pathway, and its dysfunction is associated with several neoplastic diseases. PTEN is frequently found mutated in many pathological conditions highlighting its importance in normal physiological function. Unlike several cellular proteins which are activated by phosphorylation, PTEN is inactivated upon phosphorylation by specific kinases which phosphorylate serine and threonine residues in its C-terminal region. Therefore, development of therapeutic agents that specifically target kinases and kinase-domain-containing proteins affecting PTEN would lead to the treatment of PTEN-related diseases. With increasing evidence on the role of PTEN in many human diseases, the present review focuses on the clinical relevance of PTEN with a comprehensive list of currently identified modulators of PTEN, and proposes potentially novel molecular targets which could aid in the development of drug candidates for the treatment of PTEN-related diseases such as cardiovascular diseases, diabetes, obesity, cancer, autism, Parkinson's and Alzheimer's diseases. This review describes several target sites that could help in the development of novel drug candidates to regulate or restore the normal physiological functions of PTEN and are essential in the treatment of human diseases where PTEN plays a pivotal role.

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Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Wolters Kluwer Health

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: July 2017

Publication date (Electronic): 21 July 2017

Volume: 96

Issue: 29

Electronic Location Identifier: e7111

Affiliations

[a ]Department of Oncology, Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou

[b ]Department of Pathology, People's Hospital of Puyang, Puyang, China.

Author notes

[∗ ]Correspondence: Mingzhi Zhang, Department of Oncology, Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, No.1 Jian She Road, Zhengzhou, Henan 450000, China (e-mail: mingzhi_zhang1@ 123456126.com ).

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Publisher ID: MD-D-16-07533 Accession ID: 07111

DOI: 10.1097/MD.0000000000007111

PMC ID: 5521878

PubMed ID: 28723738

SO-VID: 3d97a72d-b2f8-4219-992a-2e45e3a13aa7

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This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

History

Date received : 15 December 2016

Date revision received : 13 April 2017

Date accepted : 15 May 2017

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Keywords: ki-67,nasal-type natural killer/t-cell lymphoma,phosphatase and tensin homolog

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Keywords: ki-67, nasal-type natural killer/t-cell lymphoma, phosphatase and tensin homolog

Phosphatase and tensin homolog ( PTEN) is down-regulated in human NK/T-cell lymphoma and corrects with clinical outcomes

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Most cited references 25

Targeting nonclassical oncogenes for therapy in T-ALL.

PI3K/AKT/PTEN pathway as a target for Crohn's disease therapy (Review).

PTEN modulators: a patent review.

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