2014 Fiscal Year Final Research Report
New therapeutic strategy targeting phosphorylation sites of the PTEN C-terminus for lung epithelial/endothelial-mesenchymal transition
Project/Area Number |
24591162
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Nagoya University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Yoshinori 名古屋大学, 医学系研究科, 教授 (20270986)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Keywords | 線維症 / 肺癌 / PTEN / TGFbeta |
Outline of Final Research Achievements |
Although many pathways in the tumor microenvironment are negatively regulated by the concerted lipid and protein phosphatase activities of PTEN, pulmonary fibrosis and lung cancers often show hyperactivation of these pathways. We recently showed that TGFβ and other factors stimulation modifies both phosphorylation of PTEN on its C-terminus (p-PTEN) and total PTEN levels in lung cancer cells, and consequently leads to the loss of PTEN activities. Unphosphorylated PTEN with four alanine (Ala) substitution of the phosphorylation sites in the PTEN C-terminus (PTEN4A) rescues cells from TGFβ-induced loss of PTEN activities and the acquisition of EMT phenotypes. In this project, we demonstrated that exogenous induction of adenovirus carrying PTEN4A repressed TGFβ-induced EMT in alveolar cells. Furthermore, by structural and function analysis of PTEN, we showed that the phosphatase activity of PTEN4A depended on an essential association between the C2 and phosphatase domains.
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Free Research Field |
呼吸器内科学
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