STAT5-Dependent CyclinD1 and Bcl-xL expression in Bcr-Abl-transformed cells

Mol Cell Biol Res Commun. 2000 May;3(5):299-305. doi: 10.1006/mcbr.2000.0231.

Abstract

Signal transducers and activators of transcription (STATs) are a family of transcription factors that were originally identified as mediators of cytokine-induced gene expression. We and others have recently shown that STAT5 also plays a major role in cellular transformation by the Bcr-Abl oncogene. Here we show that the antiapoptotic bcl-xL gene product and the cell cycle regulator cyclin D1 are targets of STAT5 in Bcr-Abl-transformed cells. In the CML cell line K562 and in BaF3 cells ectopically expressing Bcr-Abl, both the cyclin D1 and bcl-x promoters are highly active. The activity of these promoters can be strongly repressed by cotransfection of a dominant negative (DN) mutant of STAT5. Moreover, the cyclin D1 and bcl-x promoters contain STAT binding sites to which STAT5 constitutively binds in Bcr-Abl transformed cells. These results suggest that STAT5 contributes to transformation by Bcr-Abl by induction of cyclin D1 and bcl-xL expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Transformation, Neoplastic*
  • Cyclin D1 / genetics*
  • Cyclin D1 / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Genes, abl / genetics*
  • Humans
  • K562 Cells
  • Milk Proteins*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Recombinant Fusion Proteins
  • STAT5 Transcription Factor
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transfection
  • Tumor Cells, Cultured
  • bcl-X Protein

Substances

  • BCL2L1 protein, human
  • DNA-Binding Proteins
  • Milk Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • STAT5 Transcription Factor
  • Trans-Activators
  • bcl-X Protein
  • Cyclin D1