The polycythemia vera-associated Jak2 V617F mutant induces tumorigenesis in nude mice

Miyuki Abe, Megumi Funakoshi-Tago, Kenji Tago, Jun Kamishimoto, Eriko Aizu-Yokota, Yoshiko Sonoda, Tadashi Kasahara

研究成果: Article査読

21 被引用数 (Scopus)

抄録

The somatic Jak2 mutation (V617F) was identified in most patients with polycythemia vera (PV). Here, we show that the activating Jak2 V617F mutant completely protected Ba/F3 cells from cytokine withdrawal-induced apoptotic cell death. Interestingly, Ba/F3 cells expressing Jak2 V617F mutant induced rapid tumorigenesis in nude mice, leading to rapid death. Whereas an injection of Ba/F3 cells expressing wild-type Jak2 had no effect, an injection of Ba/F3 cells expressing Jak2 V617F mutant promptly invaded and spread into various distinct organs, such as the liver and spleen. Strikingly, Jak2 inhibitor, AG490 potently inhibited cytokine-independent cell growth induced by the Jak2 V617F mutant. Also, treatment with AG490 effectively delayed Jak2 V617F mutant-induced tumorigenesis in nude mice. Thus, our results both in vitro and in vivo suggest that Jak2 harboring V617F mutation is a potent oncogene able to promote cell transformation and tumorigenesis.

本文言語English
ページ(範囲)870-877
ページ数8
ジャーナルInternational Immunopharmacology
9
7-8
DOI
出版ステータスPublished - 2009 7月

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学
  • 薬理学

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