Chemokine stromal cell-derived factor-1 induction by C/EBPbeta activation is associated with all-trans-retinoic acid-induced leukemic cell differentiation.
Stromal cell-derived factor-1 (SDF-1/CXCL12) is one of the essential chemokines, which mediates hematopoietic differentiations. However, the mechanism by which SDF-1 expression is regulated in granulocyte differentiation is poorly understood. Here, we suggest a novel mechanism by which all-trans-retinoic acid (ATRA) induces the expression of SDF-1 during the differentiation of promyelomonocytic leukemic U937 cells. Moreover, we also demonstrate that activation of transcription factor C/EBPbeta by ATRA regulates SDF-1 expression in U937 cells. In addition, we show that the cyclin-dependent kinase inhibitors p21(WAF1/CIP1) and Pyk2 are up-regulated by SDF-1 and increased markedly by the costimulation of ATRA and SDF-1. Furthermore, ATRA and SDF-1alpha additively induce U937 cell differentiation. Indeed, silencing the expression of SDF-1 inhibits ATRA-induced granulocyte differentiation significantly. Taken together, these results indicate that SDF-1alpha is involved in granulocyte differentiation in response to ATRA, mediated by the activation of the transcription factor C/EBPbeta.
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan, Korea.
Kyeong Jin
KJ
Kim
Hyeong Hoe
HH
Kim
Joon Hong
JH
Kim
Yung Hyun
YH
Choi
Young Hee
YH
Kim
Jae Hun
JH
Cheong
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D018925:Chemokines / Q000494:pharmacology; D047369:Chromatin Immunoprecipitation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D022782:CCAAT-Enhancer-Binding Protein-beta; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D014212:Tretinoin; D008156:Luciferases