Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells

Kazuya Sumi; Kenji Tago; Tadashi Kasahara; Megumi Funakoshi-Tago

doi:10.1016/j.febslet.2011.04.068

Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells

Kazuya Sumi, Kenji Tago, Tadashi Kasahara, Megumi Funakoshi-Tago

薬学科

研究成果: Article › 査読

33 被引用数 (Scopus)

抄録

JAK2 V617F mutant induces transformation through aberrant activation of various transcription factors. We found that the expression of Aurora kinase A (Aurka) was significantly induced by mutant JAK2 through c-Myc expression. Interestingly, mutant JAK2 enhanced resistance to cisplatin (CDDP)-induced DNA damage, and effectively suppressed apoptosis. Ectopic expression of Aurka in Ba/F3 cells exhibited similar resistance to CDDP, and this required kinase activity. Conversely, knockdown and inhibition of Aurka in cells expressing mutant JAK2 abolished the resistance to CDDP. Taken together, Aurka is most likely critical for resistance to DNA damage in cells transformed by JAK2 V617F mutant.

本文言語	English
ページ（範囲）	1884-1890
ページ数	7
ジャーナル	FEBS Letters
巻	585
号	12
DOI	https://doi.org/10.1016/j.febslet.2011.04.068
出版ステータス	Published - 2011 6月 23

ASJC Scopus subject areas

生物理学
構造生物学
生化学
分子生物学
遺伝学
細胞生物学

UN SDG

この成果は、次の持続可能な開発目標に貢献しています

文献へのアクセス

10.1016/j.febslet.2011.04.068

他のファイルとリンク

フィンガープリント

「Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル

@article{acef293a04964050b42e6f7dbc356673,

title = "Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells",

abstract = "JAK2 V617F mutant induces transformation through aberrant activation of various transcription factors. We found that the expression of Aurora kinase A (Aurka) was significantly induced by mutant JAK2 through c-Myc expression. Interestingly, mutant JAK2 enhanced resistance to cisplatin (CDDP)-induced DNA damage, and effectively suppressed apoptosis. Ectopic expression of Aurka in Ba/F3 cells exhibited similar resistance to CDDP, and this required kinase activity. Conversely, knockdown and inhibition of Aurka in cells expressing mutant JAK2 abolished the resistance to CDDP. Taken together, Aurka is most likely critical for resistance to DNA damage in cells transformed by JAK2 V617F mutant.",

keywords = "Aurora kinase A, Cisplatin, JAK2, Myeloproliferative neoplasm, V617F mutation",

author = "Kazuya Sumi and Kenji Tago and Tadashi Kasahara and Megumi Funakoshi-Tago",

note = "Funding Information: We thank Dr. J.N. Ihle for the retroviral vectors of JAK2 and EpoR. This work was supported in part by grants ( 21790090 ) from MEXT and Takeda Science Foundation . ",

year = "2011",

month = jun,

day = "23",

doi = "10.1016/j.febslet.2011.04.068",

language = "English",

volume = "585",

pages = "1884--1890",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Elsevier",

number = "12",

}

TY - JOUR

T1 - Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells

AU - Sumi, Kazuya

AU - Tago, Kenji

AU - Kasahara, Tadashi

AU - Funakoshi-Tago, Megumi

N1 - Funding Information: We thank Dr. J.N. Ihle for the retroviral vectors of JAK2 and EpoR. This work was supported in part by grants ( 21790090 ) from MEXT and Takeda Science Foundation .

PY - 2011/6/23

Y1 - 2011/6/23

N2 - JAK2 V617F mutant induces transformation through aberrant activation of various transcription factors. We found that the expression of Aurora kinase A (Aurka) was significantly induced by mutant JAK2 through c-Myc expression. Interestingly, mutant JAK2 enhanced resistance to cisplatin (CDDP)-induced DNA damage, and effectively suppressed apoptosis. Ectopic expression of Aurka in Ba/F3 cells exhibited similar resistance to CDDP, and this required kinase activity. Conversely, knockdown and inhibition of Aurka in cells expressing mutant JAK2 abolished the resistance to CDDP. Taken together, Aurka is most likely critical for resistance to DNA damage in cells transformed by JAK2 V617F mutant.

AB - JAK2 V617F mutant induces transformation through aberrant activation of various transcription factors. We found that the expression of Aurora kinase A (Aurka) was significantly induced by mutant JAK2 through c-Myc expression. Interestingly, mutant JAK2 enhanced resistance to cisplatin (CDDP)-induced DNA damage, and effectively suppressed apoptosis. Ectopic expression of Aurka in Ba/F3 cells exhibited similar resistance to CDDP, and this required kinase activity. Conversely, knockdown and inhibition of Aurka in cells expressing mutant JAK2 abolished the resistance to CDDP. Taken together, Aurka is most likely critical for resistance to DNA damage in cells transformed by JAK2 V617F mutant.

KW - Aurora kinase A

KW - Cisplatin

KW - JAK2

KW - Myeloproliferative neoplasm

KW - V617F mutation

UR - http://www.scopus.com/inward/record.url?scp=79958117200&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958117200&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2011.04.068

DO - 10.1016/j.febslet.2011.04.068

M3 - Article

C2 - 21557940

AN - SCOPUS:79958117200

SN - 0014-5793

VL - 585

SP - 1884

EP - 1890

JO - FEBS Letters

JF - FEBS Letters

IS - 12

ER -