Ran GTPase protein promotes human pancreatic cancer proliferation by deregulating the expression of Survivin and cell cycle proteins.
Ran, a member of the Ras GTPase family, has important roles in nucleocytoplasmic transport. Herein, we detected Ran expression in pancreatic cancer and explored its potential role on tumour progression. Overexpressed Ran in pancreatic cancer tissues was found highly correlated with the histological grade. Downregulation of Ran led to significant suppression of cell proliferation, cell cycle arrest at the G1/S phase and induction of apoptosis. In vivo studies also validated that result. Further studies revealed that those effects were at least partly mediated by the downregulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, CDK4, phospho-Rb and Survivin proteins and up regulation of cleaved Caspase-3.
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
Lin
L
Deng
Yuanyuan
Y
Lu
Xiaodi
X
Zhao
Yi
Y
Sun
Yongquan
Y
Shi
Hongwei
H
Fan
Changhao
C
Liu
Jinfeng
J
Zhou
Yongzhan
Y
Nie
Kaichun
K
Wu
Daiming
D
Fan
Xuegang
X
Guo
D000818:Animals; D053148:Caspase 3 / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D016196:S Phase / Q000187:drug effects; D000077022:Survivin; D020931:ran GTP-Binding Protein / Q000096:biosynthesis / Q000502:physiology*
C107489:BIRC5 protein, human; D018797:Cell Cycle Proteins; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D053148:Caspase 3; D020931:ran GTP-Binding Protein
Cell cycle; Pancreatic cancer; Proliferation; Ran; Survivin