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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2246-2257
Number of pages12
JournalLeukemia
Volume21
Issue number11
DOIs
Publication statusPublished - 2007 Nov
Externally publishedYes

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Protein-Tyrosine Kinases
Clone Cells
Neoplasms
Leukemia
4'-N-benzoylstaurosporine
Transforming Growth Factors
Growth
Transcriptome
Point Mutation
Acute Myeloid Leukemia
Small Interfering RNA
Monocytes
Phosphotransferases
Cell Line
Mutation

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Lu, Y., Kitaura, J., Oki, T., Komeno, Y., Ozaki, K., Kiyono, M., ... Kitamura, T. (2007). Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD. Leukemia, 21(11), 2246-2257. https://doi.org/10.1038/sj.leu.2404883

Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD. / Lu, Y.; Kitaura, J.; Oki, T.; Komeno, Y.; Ozaki, K.; Kiyono, M.; Kumagai, H.; Nakajima, H.; Nosaka, T.; Aburatani, H.; Kitamura, T.

In: Leukemia, Vol. 21, No. 11, 11.2007, p. 2246-2257.

Research output: Contribution to journalArticle

Lu, Y, Kitaura, J, Oki, T, Komeno, Y, Ozaki, K, Kiyono, M, Kumagai, H, Nakajima, H, Nosaka, T, Aburatani, H & Kitamura, T 2007, 'Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD', Leukemia, vol. 21, no. 11, pp. 2246-2257. https://doi.org/10.1038/sj.leu.2404883
Lu, Y. ; Kitaura, J. ; Oki, T. ; Komeno, Y. ; Ozaki, K. ; Kiyono, M. ; Kumagai, H. ; Nakajima, H. ; Nosaka, T. ; Aburatani, H. ; Kitamura, T. / Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD. In: Leukemia. 2007 ; Vol. 21, No. 11. pp. 2246-2257.
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AU - Ozaki, K.

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