Open AccessPer2 Is a C/EBP Target Gene Implicated in Myeloid Leukemia
Author(s) -
Sigal Gery,
H. Phillip Koeffler
Publication year - 2009
Publication title -
integrative cancer therapies
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 60
eISSN - 1552-695X
pISSN - 1534-7354
DOI - 10.1177/1534735409352084
Subject(s) - per2 , myeloid leukemia , biology , myeloid , clonogenic assay , circadian rhythm , cancer research , haematopoiesis , leukemia , endogeny , chronic myelogenous leukemia , transcription factor , apoptosis , microbiology and biotechnology , circadian clock , immunology , endocrinology , stem cell , gene , clock , genetics
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-Erbα, 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.