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

Tamihiro Kamata, Yutaka Hattori, Hirofumi Hamada, Masahiro Kizaki, Masaaki Terada, Yasuo Ikeda

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)297-305
Number of pages9
JournalExperimental Hematology
Volume30
Issue number4
DOIs
Publication statusPublished - 2002

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Fibroblast Growth Factor 7
Cell Differentiation
Genes
Bone Marrow Cells
Phosphorylation
Cell Proliferation
Cell Line
Gene Targeting
Short Stature, Auditory Canal Atresia, Mandibular Hypoplasia, Skeletal Abnormalities
Granulocyte Colony-Stimulating Factor
Genetic Therapy
Stem Cells
Therapeutics
Epithelial Cells
Observation
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Keratinocyte growth factor regulates proliferation and differentiation of hematopoietic cells expressing the receptor gene K-sam. / Kamata, Tamihiro; Hattori, Yutaka; Hamada, Hirofumi; Kizaki, Masahiro; Terada, Masaaki; Ikeda, Yasuo.

In: Experimental Hematology, Vol. 30, No. 4, 2002, p. 297-305.

Research output: Contribution to journalArticle

Kamata, Tamihiro ; Hattori, Yutaka ; Hamada, Hirofumi ; Kizaki, Masahiro ; Terada, Masaaki ; Ikeda, Yasuo. / Keratinocyte growth factor regulates proliferation and differentiation of hematopoietic cells expressing the receptor gene K-sam. In: Experimental Hematology. 2002 ; Vol. 30, No. 4. pp. 297-305.
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AU - Ikeda, Yasuo

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