Rap1GAP alters leukemia cell differentiation, apoptosis and invasion in vitro

Qiu,Tingting; Qi,Xiaofei; Cen,Jiannong; Chen,Zixing

doi:10.3892/or.2012.1825

Rap1GAP alters leukemia cell differentiation, apoptosis and invasion in vitro

Authors:
- Tingting Qiu
- Xiaofei Qi
- Jiannong Cen
- Zixing Chen
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Affiliations: Leukemia Research Unit, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Institute of Hematology, First Afﬁliated Hospital, Soochow University, Suzhou 215006, P.R. China
Published online on: May 18, 2012 https://doi.org/10.3892/or.2012.1825
Pages: 622-628

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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.

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