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INVOLVEMENT OF KRAS G12A MUTATION IN THE IL-2-INDEPENDENT GROWTH OF A HUMAN T-LGL LEUKEMIA CELL LINE, PLT-2
https://doi.org/10.18999/nagjms.74.3-4.261
https://doi.org/10.18999/nagjms.74.3-4.261121672d7-eb99-42f2-a2a6-6d18b46fbdd6
名前 / ファイル | ライセンス | アクション |
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05_Mizutani.pdf (489.1 kB)
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Item type | 紀要論文 / Departmental Bulletin Paper(1) | |||||
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公開日 | 2012-08-29 | |||||
タイトル | ||||||
タイトル | INVOLVEMENT OF KRAS G12A MUTATION IN THE IL-2-INDEPENDENT GROWTH OF A HUMAN T-LGL LEUKEMIA CELL LINE, PLT-2 | |||||
言語 | en | |||||
著者 |
MIZUTANI, NAOKI
× MIZUTANI, NAOKI× ITO, HIROMI× HAGIWARA, KAZUMI× KOBAYASHI, MISA× HOSHIKAWA, ASUKA× NISHIDA, YAYOI× TAKAGI, AKIRA× KOJIMA, TETSUHITO× SUZUKI, MOTOSHI× OSAWA, YOSUKE× OHNISHI, KAZUNORI× DAIBATA, MASANORI× MURATE, TAKASHI |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Human LGL leukemia cell lines | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | MOTN-1 and PLT-2 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | IL-2 independent growth | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Ras/MAP/ERK pathway | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | KRAS G12A mutation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Ras activity | |||||
抄録 | ||||||
内容記述 | Cytokine-dependent cell lines have been used to analyze the cytokine-induced cellular signaling and the mechanism of oncogenesis. In the current study, we analyzed MOTN-1 and PLT-2 cell lines established from different stages of a T-cell large granular lymphocyte leukemia patient (Daibata et al. 2004). MOTN-1 is IL-2-dependent derived from the chronic phase, whereas IL-2-independent PLT-2 is from the aggressive and terminal stage. They shared considerable chromosome abnormalities and the pattern of T-cell receptor rearrangement, presuming that the cytokine independence of PLT-2 was due to the additive genetic abnormality. Besides IL-2, IL-15 supported MOTN-1 cell growth, because these receptors share b- and g-subunits. IL-2 activated ERK, AKT and STAT pathway of MOTN-1. STAT3 pathway of PLT-2 was also activated by IL-2, suggesting intact IL-2 induces signal transduction of PLT-2. However, ERK1/2 but not AKT, was continuously activated in PLT-2, consistent with the increased Ras-activity of PLT-2. Sequence analysis revealed KRAS G12A mutation but not NRAS and HRAS mutation of PLT-2 but not MOTN-1. Another signaling molecule affecting Ras-signaling pathway, SHP2, which has been frequently mutated in juvenile myelomonocytic leukemia (JMML), did not show mutation. Moreover, MEK inhibitor, PD98059, as well as farnesylation inhibitor inhibited PLT-2 cell growth. Using NIH3T3 and MOTN-1, ERK activation, increased cell proliferation and survival by KRAS G12A were shown, suggesting the important role of KRAS G12A in IL-2-independent growth of PLT-2. Taken together, KRAS G12A is important for IL-2-independent growth of PLT-2 cells and suggests the possibility of involvement of KRAS mutation with disease progression. | |||||
言語 | en | |||||
内容記述タイプ | Abstract | |||||
出版者 | ||||||
言語 | en | |||||
出版者 | Nagoya University School of Medicine | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | departmental bulletin paper | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
ID登録 | ||||||
ID登録 | 10.18999/nagjms.74.3-4.261 | |||||
ID登録タイプ | JaLC | |||||
関連情報 | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | URI | |||||
関連識別子 | http://www.med.nagoya-u.ac.jp/medlib/nagoya_j_med_sci/7434/7434.html | |||||
ISSN(print) | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0027-7622 | |||||
ISSN(Online) | ||||||
収録物識別子タイプ | EISSN | |||||
収録物識別子 | 2186-3326 | |||||
書誌情報 |
en : Nagoya Journal of Medical Science 巻 74, 号 3-4, p. 261-271, 発行日 2012-08 |
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著者版フラグ | ||||||
値 | publisher | |||||
URI | ||||||
識別子 | http://hdl.handle.net/2237/16737 | |||||
識別子タイプ | HDL |