CacyBP/SIP protein promotes proliferation and G1/S transition of human pancreatic cancer cells.
Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP), a component of the ubiquitin-mediated proteolysis, could participate in beta-catenin degradation, which was found to be related to the malignant phenotypes of pancreatic cancer previously. However, the role of CacyBP/SIP itself in pancreatic cancer has not been investigated. In the present study, CacyBP/SIP expression was assayed and manipulated to reveal the potential mechanism in pancreatic cancer carcinogenesis. Here, we show that CacyBP/SIP is over-expressed in pancreatic cancer cells. Down-regulation of CacyBP/SIP by small interference RNA (siRNA) severely suppresses the proliferation and tumorigenesis in pancreatic cancer. G1/S transition arrest induced by inhibition of CacyBP/SIP is at least partly mediated by down-regulation of Cyclin E and CDK2 as well as up-regulation of p27 and Rb. Collectively, CacyBP/SIP as an enhancer of pancreatic cancer malignance might develop into another possible therapeutic target.
State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China.
Xiong
X
Chen
Ping
P
Mo
Xiaohua
X
Li
Peichan
P
Zheng
Lina
L
Zhao
Zengfu
Z
Xue
Gui
G
Ren
Guohong
G
Han
Xin
X
Wang
Daiming
D
Fan
D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D016160:Retinoblastoma Protein / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000235:genetics / Q000502:physiology*; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C491778:CACYBP protein, human; D002135:Calcium-Binding Proteins; D019927:Cyclin E; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051357:Cyclin-Dependent Kinase 2