The role of CREB as a proto-oncogene in hematopoiesis and in acute myeloid leukemia.
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.
Shankar
Deepa B
DB
Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories and Mattel Children's Hospital, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Cheng
Jerry C
JC
Kinjo
Kentaro
K
Federman
Noah
N
Moore
Theodore B
TB
Gill
Amandip
A
Rao
Nagesh P
NP
Landaw
Elliot M
EM
Sakamoto
Kathleen M
KM
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000208:Acute Disease; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein; D019925:Cyclin A / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007958:Leukocyte Count; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D013154:Spleen / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics
C435500:ABCC11 protein, human; D018528:ATP-Binding Cassette Transporters; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D019925:Cyclin A; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering; D014157:Transcription Factors