Cell Biology and Toxicology

, Volume 28, Issue 4, pp 201–212

Ectopic expression of Flt3 kinase inhibits proliferation and promotes cell death in different human cancer cell lines

  • Eystein Oveland
  • Line Wergeland
  • Randi Hovland
  • James B. Lorens
  • Bjørn Tore Gjertsen
  • Kari E. Fladmark
Original Research

DOI: 10.1007/s10565-012-9216-z

Cite this article as:
Oveland, E., Wergeland, L., Hovland, R. et al. Cell Biol Toxicol (2012) 28: 201. doi:10.1007/s10565-012-9216-z

Abstract

Stable ectopic expression of Flt3 receptor tyrosine kinase is usually performed in interleukin 3 (IL-3)-dependent murine cell lines like Ba/F3, resulting in loss of IL-3 dependence. Such high-level Flt3 expression has to date not been reported in human acute myeloid leukemia (AML) cell lines, despite the fact that oncogenic Flt3 aberrancies are frequent in AML patients. We show here that ectopic Flt3 expression in different human cancer cell lines might reduce proliferation and induce apoptotic cell death, involving Bax/Bcl2 modulation. Selective depletion of Flt3-expressing cells occurred in human AML cell lines transduced with retroviral Flt3 constructs, shown here using the HL-60 leukemic cell line. Flt3 expression was investigated in two cellular model systems, the SAOS-2 osteosarcoma cell line and the human embryonic kidney HEK293 cell line, and proliferation was reduced in both systems. HEK293 cells underwent apoptosis upon ectopic Flt3 expression and cell death could be rescued by overexpression of Bcl-2. Furthermore, we observed that the Flt3-induced inhibition of proliferation in HL-60 cells appeared to be Bax-dependent. Our results thus suggest that excessive Flt3 expression has growth-suppressive properties in several human cancer cell lines.

Keywords

Acute myeloid leukemiaCell deathFlt3Receptor tyrosine kinase

Abbreviations

AML

Acute myeloid leukemia

Flt3ITD

Flt3 with internal tandem duplication

IL-3

Interleukin 3

RTK

Receptor tyrosine kinase

wt

Wild type

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Eystein Oveland
    • 1
    • 2
  • Line Wergeland
    • 3
    • 5
  • Randi Hovland
    • 4
    • 6
  • James B. Lorens
    • 2
  • Bjørn Tore Gjertsen
    • 5
    • 3
  • Kari E. Fladmark
    • 6
  1. 1.Proteomics Unit at University of Bergen (PROBE)University of BergenBergenNorway
  2. 2.Department of BiomedicineUniversity of BergenBergenNorway
  3. 3.Department of Medicine, Hematology SectionHaukeland University HospitalBergenNorway
  4. 4.Center for Medical Genetics and Molecular MedicineHaukeland University HospitalBergenNorway
  5. 5.Institute of Medicine, Hematology SectionUniversity of BergenBergenNorway
  6. 6.Department of Molecular BiologyUniversity of BergenBergenNorway