The role of CREB as a proto-oncogene in hematopoiesis and in acute myeloid leukemia

Cancer Cell. 2005 Apr;7(4):351-62. doi: 10.1016/j.ccr.2005.02.018.

Abstract

CREB is a transcription factor that functions in glucose homeostasis, growth factor-dependent cell survival, and memory. In this study, we describe a role of CREB in human cancer. CREB overexpression is associated with increased risk of relapse and decreased event-free survival. CREB levels are elevated in blast cells from patients with acute myeloid leukemia. To understand the role of CREB in leukemogenesis, we studied the biological consequences of CREB overexpression in primary human leukemia cells, leukemia cell lines, and transgenic mice. Our results demonstrate that CREB promotes abnormal proliferation and survival of myeloid cells in vitro and in vivo through upregulation of specific target genes. Thus, we report that CREB is implicated in myeloid cell transformation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Acute Disease
  • Animals
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Cell Survival / physiology
  • Cyclic AMP Response Element-Binding Protein
  • Cyclin A / metabolism
  • Down-Regulation / genetics
  • Gene Expression / genetics
  • Hematopoiesis / physiology*
  • Humans
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / physiopathology*
  • Leukocyte Count
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / metabolism
  • Myeloproliferative Disorders / pathology
  • Phosphorylation
  • Proto-Oncogenes / genetics
  • Proto-Oncogenes / physiology*
  • RNA, Small Interfering / genetics
  • Spleen / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transfection
  • Tumor Cells, Cultured
  • Up-Regulation / genetics

Substances

  • ABCC11 protein, human
  • ATP-Binding Cassette Transporters
  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Cyclin A
  • RNA, Small Interfering
  • Transcription Factors