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

5 Citations (Scopus)

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

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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