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

研究成果: Article査読

5 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)297-305
ページ数9
ジャーナルExperimental Hematology
30
4
DOI
出版ステータスPublished - 2002

ASJC Scopus subject areas

  • 分子生物学
  • 血液学
  • 遺伝学
  • 細胞生物学
  • 癌研究

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