Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD

Y. Lu, J. Kitaura, T. Oki, Y. Komeno, K. Ozaki, M. Kiyono, H. Kumagai, H. Nakajima, T. Nosaka, H. Aburatani, T. Kitamura

研究成果: Article査読

20 被引用数 (Scopus)

抄録

Transforming growth factor-β (TGF-β)-stimulated clone-22 (TSC-22) was originally isolated as a TGF-β-inducible gene. In this study, we identified TSC-22 as a potential leukemia suppressor. Two types of FMS-like tyrosine kinase-3 (Flt3) mutations are frequently found in acute myeloid leukemia: Flt3-ITD harboring an internal tandem duplication in the juxtamembrane domain associated with poor prognosis and Flt3-TKD harboring a point mutation in the kinase domain. Comparison of gene expression profiles between Flt3-ITD- and Flt3-TKD-transduced Ba/F3 cells revealed that constitutive activation of Flt3 by Flt3-TKD, but not Flt3-ITD, upregulated the expression of TSC-22. Importantly, treatment with an Flt3 inhibitor PKC412 or an Flt3 small interfering RNA decreased the expression level of TSC-22 in Flt3-TKD-transduced cells. Forced expression of TSC-22 suppressed the growth and accelerated the differentiation of several leukemia cell lines into monocytes, in particular, in combination with differentiation-inducing reagents. On the other hand, a dominant-negative form of TSC-22 accelerated the growth of Flt3-TKD-transduced 32Dcl.3 cells. Collectively, these results suggest that TSC-22 is a possible target of leukemia therapy.

本文言語English
ページ(範囲)2246-2257
ページ数12
ジャーナルLeukemia
21
11
DOI
出版ステータスPublished - 2007 11
外部発表はい

ASJC Scopus subject areas

  • 血液学
  • 腫瘍学
  • 癌研究

フィンガープリント

「Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD」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