Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells

C. Weinstein-Oppenheimer, L. S. Steelman, P. A. Algate, W. L. Blalock, C. Burrows, P. E. Hoyle, J. T. Lee, P. W. Moye, J. G. Shelton, R. Franklin, J. A. McCubrey

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of deregulated Raf activation on the growth and differentiation of hematopoietic cells were investigated. The cytokine-dependent murine myeloid FDC-P1 and human erythroleukemic TF-1 cell lines were transformed to grow in response to deregulated Raf expression in the absence of exogenous cytokines. The conditionally active Raf proteins were regulated by β-estradiol as cDNAs containing the Raf catalytic, but lacking negative-regulatory domains, were ligated to the hormone binding domain of the estrogen receptor (ΔRaf:ER). Continuous ΔRaf expression prevented apoptosis in the absence of exogenous cytokines and altered the morphology of the FD/ΔRaf:ER cells as they grew in large aggregated masses (>100 cells) whereas the parental cytokine-dependent FDC-P1 cells grew in smaller grape-like clusters (3H-thymidine incorporation in response to GM-CSF. Interestingly, Raf activation counterbalanced the inhibition of DNA synthesis caused by RA but not PMA. Thus deregulated Raf expression can alter cytokine dependency, integrin expression and the stage of differentiation. These Raf-responsive cell lines will be useful in elucidating the roles of the MAP kinase cascade on hematopoietic cell differentiation and malignant transformation.

Original languageEnglish
Pages (from-to)1921-1938
Number of pages18
JournalLeukemia
Volume14
Issue number11
Publication statusPublished - 2000

Keywords

  • Apoptosis
  • Autocrine transformation
  • Differentiation
  • GM-CSF expression
  • Integrins
  • Raf

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

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