Pim-1 expression is sufficient to induce cytokine independence in murine hematopoietic cells, but is dispensable for BCR-ABL-mediated transformation

Exp Hematol. 2002 Jul;30(7):697-702. doi: 10.1016/s0301-472x(02)00808-1.

Abstract

Objective: BCR-ABL is a unique oncoprotein of which sole expression can cause cancer. A number of signaling molecules were shown to be activated by BCR-ABL. One of the important molecules that contributes to BCR-ABL-mediated cell proliferation is signal transducer and activator of transcription (STAT) 5. To elucidate the mechanism of BCR-ABL-mediated leukemogenesis, a role of pim-1, one of the important target genes of STAT5, was investigated.

Materials and methods: A temperature-sensitive mutant of p210(BCR-ABL) was introduced in interleukin-3-dependent murine hematopoietic cell line Ba/F3 cells, and downstream signaling after activation of BCR-ABL was investigated. Effects of the expression of a dominant-negative (dn) Pim-1 and a dn STAT5A in BCR-ABL-driven cell proliferation also were studied in Ba/F3 cells.

Results: We found that pim-1 was markedly up-regulated following activation of BCR-ABL tyrosine kinase with activation of STAT5. Overexpression of pim-1 alone induced cytokine-independent cell growth of Ba/F3 cells in a dose-dependent manner. However, expression of the dn Pim-1 did not affect growth of Ba/F3 cells transformed by BCR-ABL, whereas that of the dn STAT5A did suppress it.

Conclusion: Pim-1 is one of the redundant molecules that contributes to induction of autonomous cell growth and is dispensable for leukemogenesis by BCR-ABL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Line / drug effects
  • Cell Transformation, Neoplastic / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / physiology*
  • Gene Dosage
  • Genes, Dominant
  • Hematopoietic Stem Cells / enzymology*
  • Hematopoietic Stem Cells / pathology
  • Interleukin-3 / pharmacology
  • Mice
  • Milk Proteins*
  • Mutagenesis, Site-Directed
  • Mutation
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Protein Isoforms / physiology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-pim-1
  • Recombinant Fusion Proteins / physiology
  • STAT5 Transcription Factor
  • Signal Transduction / physiology
  • Temperature
  • Trans-Activators / genetics
  • Trans-Activators / physiology

Substances

  • DNA-Binding Proteins
  • Interleukin-3
  • Milk Proteins
  • Neoplasm Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • STAT5 Transcription Factor
  • Stat5a protein, mouse
  • Trans-Activators
  • Fusion Proteins, bcr-abl
  • Pim1 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1