title: Rap1GAP alters leukemia cell differentiation, apoptosis and invasion             in vitro.
abstract: Rap1GAP which regulates the GTP-GDP form switch of Rap1 is a member of the             GTPase-activating protein (GAP) family and has recently received substantial attention.             Rap1GAP is thought of as a putative tumor suppressor gene and plays an important             role in human tumor progression including pancreatic cancer, thyroid cancer and             melanoma. In the current study, we found that the expression of Rap1GAP was lower             in acute myeloid leukemia (AML) patients compared to non-malignant blood disease             patients. The expression of Rap1GAP was also low in HL-60, NB4, U937 and SHI-1             myeloid leukemia cell lines. Upregulated Rap1GAP in NB4 and HL-60 cells promoted             cell differentiation induced by ATRA or TPA compared to the empty vector control             cells. Furthermore, Rap1GAP-transfected cells also showed a higher rate of apoptosis             in response to arsenic trioxide compared to the control counterpart cells. In             addition, we found that increased expression of Rap1GAP promoted leukemia cell             invasion may be due to matrix metalloproteinase 9 (MMP9). In conclusion, these             results demonstrated that Rap1GAP promoted leukemia cell differentiation and apoptosis,             but increased leukemia cell invasion in vitro.
authors.affiliation: Leukemia Research Unit, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Institute of Hematology, First Afﬁliated Hospital, Soochow University, Suzhou 215006, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Qiu
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Qi
authors.forename: Jiannong
authors.initials: J
authors.lastname: Cen
authors.forename: Zixing
authors.initials: Z
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D015536:Down-Regulation; D020690:GTPase-Activating Proteins / Q000096:biosynthesis* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D020690:GTPase-Activating Proteins; C484658:RAP1GAP protein, human; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D020780:Matrix Metalloproteinase 9