Keratinocyte growth factor regulates proliferation and differentiation of hematopoietic cells expressing the receptor gene K-sam

Exp Hematol. 2002 Apr;30(4):297-305. doi: 10.1016/s0301-472x(01)00800-1.


Objective: The aim of this study was to establish a new method to overcome the problems of gene therapy targeting hematopoietic cells, namely low transduction efficiency and induction of differentiation during cytokine treatment.

Materials and methods: The K-sam gene encoding the receptor for keratinocyte growth factor (KGF) was transduced to three factor-dependent hematopoietic cell lines (Ba/F3, 32Dcl3, and UT-7/GM) using retroviral vector, and their proliferation, differentiation, and intracellular signaling were studied. This gene also was transduced to murine bone marrow cells, and proliferation of colony-forming cells (CFCs) by KGF stimulation was examined.

Results: Although KGF is known to target only epithelial cells, all of the three cell lines transduced with K-sam proliferated due to KGF stimulation. Morphologic observation showed that KGF induced proliferation but did not cause significant differentiation of 32D/K-sam cells. KGF treatment increased phosphorylation of ERK1/2 but did not activate STAT molecules. Granulocyte colony-stimulating factor transduced the differentiation signal with the phosphorylation of STAT3 without significant ERK1/2 activation. Proliferation by KGF of murine primary bone marrow cells transduced with K-sam then was examined in liquid culture. KGF treatment significantly increased production of CFCs derived from K-sam-transduced bone marrow cells without causing the exhaustion of immature CFCs.

Conclusions: KGF could efficiently induce proliferation of hematopoietic cells expressing the K-sam gene without obvious induction of differentiation or exhaustion of immature progenitor cells. The in vitro data are important for further preclinical in vivo study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation / drug effects
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors / pharmacology*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation / drug effects
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism
  • Receptors, Fibroblast Growth Factor / physiology*
  • STAT3 Transcription Factor
  • Signal Transduction
  • Trans-Activators / metabolism
  • Transduction, Genetic
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • FGF7 protein, human
  • Fgf7 protein, mouse
  • Receptors, Fibroblast Growth Factor
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • Trans-Activators
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors
  • FGFR2 protein, human
  • Fgfr2 protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 2
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases