Per2 is a C/EBP target gene implicated in myeloid leukemia.
Circadian rhythms are endogenous biological clocks that govern fundamental physiological and behavioral functions. Consequently, perturbations of these rhythms have been associated with pathogenic conditions, such as depression, diabetes, and cancer. CCAAT/enhancer-binding proteins (C/EBPs) are a family of transcription factors that regulate cell growth and differentiation in various tissues and have also been implicated in many cancer types. Using expression profiling studies, we found that the levels of 2 core components of the circadian network, Per2 and Rev-Erb alpha, are significantly altered by C/EBPs. Further studies showed that levels of Per2 were reduced in lymphoma and acute myeloid leukemia patient samples, as well as in lymphoma cell lines. Overexpression of Per2 in hematopoietic cancer cell lines resulted in growth inhibition, cell cycle arrest, apoptosis and loss of clonogenic ability. These results support the emerging role of circadian genes in tumor suppression.
Gery
Sigal
S
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Koeffler
H Phillip
HP
D000818:Animals; D017209:Apoptosis; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002940:Circadian Rhythm; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; C064353:NR1D1 protein, human; C498262:Nr1d1 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C421902:PER2 protein, human; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins