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PI3K/AKT/PTEN Signaling as a Molecular Target in Leukemia Angiogenesis

By Naoko Okumura, Hitomi Yoshida, Yasuko Kitagishi, Mutsumi Murakami, Yuri Nishimura and Satoru Matsuda


PI3K/AKT/PTEN pathway is important in the regulation of angiogenesis mediated by vascular endothelial growth factor in many tumors including leukemia. The signaling pathway is activated in leukemia patients as well as leukemia cell lines together with a decrease in the expression of PTEN gene. The mechanism by which the signaling pathway regulates angiogenesis remains to be further elucidated. However, it has become an attractive target for drug therapy against leukemia, because angiogenesis is a key process in malignant cell growth. In this paper, we will focus on the roles and mechanisms of PI3K/AKT/PTEN pathway in regulating angiogenesis

Topics: Review Article
Publisher: Hindawi Publishing Corporation
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    1. (2005). 3-Phosphoinositidedependent protein kinase-1-mediated IκB kinase β(IKKB) phosphorylation activates NF-κB signaling,”
    2. (2008). AKT signaling in regulating angiogenesis,”
    3. (2005). Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo,”
    4. (2009). Angiogenesis and ovarian cancer,”
    5. (2008). Angiogenesis selectively requires the p110α isoform of PI3K to control endothelial cell migration,”
    6. (2011). Anti-angiogenic activity and intracellular distribution of epigallocatechin-3-gallate analogs,”
    7. binding proteins as targets in anticancer therapy,”
    8. (2008). Differential expression of PTEN-targeting microRNAs miR-19a and miR-21 in cowden syndrome,”
    9. (2009). Endothelial nitric oxide synthase phosphorylation in treadmill-running mice: role of vascular signalling kinases,”
    10. (2011). Ethanol extract of Rosemary repressed PTEN expression
    11. (2006). Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase,”
    12. (2011). Grb-2-associated binder 1 (Gab1) regulates postnatal ischemic and VEGF-induced angiogenesis through the protein kinase
    13. (2011). GSK3β: a signaling pathway node modulating neural stem cell and endothelial cell interactions,” Angiogenesis,v o l .1 4 ,n o .2 ,p p .
    14. (2011). h a n g ,H .T a n g ,J .C a ie ta l . ,“ O v a r i a nc a n c e r - a s s o c i a t e d fibroblastscontributetoepithelialovariancarcinomametastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion,”
    15. (2010). h o w ,M .B a n ,H .L .W ue ta l .
    16. (2006). i a ,Q .M e n g ,Z .C a o ,X .S h i ,a n dB .H .J i a n g ,“ R e g u l a t i o n of aneiogenesis and tumor growth by p110 alpha and AKT1 via VEGF expression,”
    17. (2007). Identification of the JNK signaling pathway as a functional target of the tumor suppressor
    18. (2010). In vitro angiogenesis: endothelial cell tubeformation on gelled basement membrane extract,”
    19. (2005). Inhibition of the phosphatidylinositol 3-kinase/Akt pathway by inositol pentakisphosphate results in antiangiogenic and antitumor effects,”
    20. (2007). Lactate adversely affects the in vitro formation of endothelial cell tubular structures through the action of TGF-β1,” Experiment a lC e l lR e s e a r c h ,
    21. (1987). Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma,”
    22. (2006). Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy,”
    23. (2010). Osteoclast-derived matrix metalloproteinase-9 directly affects angiogenesis in the prostate tumor-bone microenvironment,”
    24. (2008). P a l l e r o ,C .A .E l z i e
    25. (2010). Pathological angiogenesis facilitates tumor cell dissemination and metastasis,” Cell Cycle,v o l .9 ,n o .5 ,p p .
    26. (2010). Perifosine inducescellcyclearrestandapoptosisinhumanhepatocellular carcinoma cell lines by blockade of Akt phosphorylation,”
    27. (2008). Phosphatidylinositol 3-kinase inhibitors: promising drug candidates for cancer therapy,”
    28. (2000). Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells,”
    29. (2009). PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CA9 and VEGF, in human cancer cell lines,”
    30. (2011). Posttranscriptional deregulation of MYC via PTEN constitutes a major alternative pathway of MYC activation in T-cell acute lymphoblastic leukemia,”
    31. PTEN’s regulation of VEGF and VEGFR1 expression and its clinical significance in myeloid leukemia,” Medical Oncology.
    32. (2005). PWT-458, a novel pegylated-17-hydroxywortmannin, inhibits phosphatidylinositol 3-kinase signaling and suppresses growth of solid tumors,”
    33. (2000). r o n e r ,K .E y b r e c h t s ,a n dJ .W .N .A k k e r m a n ,“ D u a l regulation of platelet protein kinase
    34. (2008). Resveratrol: a multitargetedagentforage-associatedchronicdiseases,”Cell Cycle,vol.
    35. (2003). S u ,L .D .M a y o ,D .B .D o n n e r ,a n dD .L .D u r d e n ,“
    36. (2005). Serum evaluation of angiogenic cytokines basic fibroblast growth factor, hepatocyte growth factor and TNF-alpha in patients with myelodysplastic syndromes: correlation with bone marrow microvascular density,”
    37. (2010). Targeting CK2 overexpression and hyperactivation as a novel therapeutic tool in chronic lymphocytic leukemia,”
    38. (2010). Targeting the translational machinery as a novel treatment strategy for hematologic malignancies,”
    39. (2009). Targeting tumor angiogenesis with histone deacetylase inhibitors,”
    40. (2011). TGFBR1 signaling and breast
    41. (2008). The nuclear affairs of PTEN,”
    42. (2010). The PI3K pathway as drug target in human cancer,”
    43. (2006). The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including
    44. (2012). Tsentelierou et al., “Immunohistochemical study of the angiogenetic network of VEGF, HIF1α, VEGFR-2 and endothelial nitric oxide synthase (eNOS)
    45. (2003). Tuberous Sclerosis Complex gene products,
    46. (2004). Vascular endothelial growth factor transcriptional activation is mediated by hypoxia-inducible factor 1α,H

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