NR AXFO
AU Liang,J.; Pan,Y.; Zhang,D.; Guo,C.; Shi,Y.; Wang,J.; Chen,Y.; Wang,X.; Liu,J.; Guo,X.; Chen,Z.; Qiao,T.; Fan,D.
TI Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS
QU The FASEB Journal 2007 Jul; 21(9): 2247-56
PT journal article
AB The function of cellular prion protein (PrPc), the essential protein for the pathogenesis and transmission of prion diseases, is still largely unknown. The putative roles of PrPc are thought to be related to cell signaling, survival, and differentiation. In a previous study, we showed that PrPc was overexpressed in gastric cancer tissues. In the present report, we show that ectopic expression of PrPc could promote tumorigenesis, proliferation, and G1/S transition in gastric cancer cells. Furthermore, CyclinD1, a protein related to cell cycle, was shown to be significantly up-regulated by PrPc at both mRNA and protein levels. PI3K/Akt pathway mediated above PrPc signal since PrPc increased the expression of phosphorylated Akt, and the specific inhibitor of Akt, LY294002, could markedly suppress growth of SGC7901 and transactivation of CyclinD1 induced by PrPc. Octapeptide repeat region played a vital role in this function, as deletion of this region abolished or reduced these effects. Collectively, this study demonstrates that overexpression of PrPc might promote the tumorigenesis and proliferation of gastric cancer cells at least partially through activation of PI3K/Akt pathway and subsequent transcriptional activation of CyclinD1 to regulate the G1/S phase transition, in which octapeptide repeat region might be an indispensable region.
MH 1-Phosphatidylinositol 3-Kinase/physiology; Animals; Cell Division/drug effects; Cell Line, Tumor; Cell Transformation, Neoplastic/genetics; Chromones/pharmacology; Cyclins/biosynthesis/genetics/physiology; G1 Phase; Gene Expression Regulation, Neoplastic/drug effects; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Morpholines/pharmacology; Neoplasm Proteins/biosynthesis/genetics/*physiology; Neoplasm Transplantation; PrPc Proteins/chemistry/genetics/*physiology; Proto-Oncogene Proteins c-akt/antagonists & inhibitors/physiology; RNA, Messenger/biosynthesis/genetics; RNA, Neoplasm/biosynthesis/genetics; Recombinant Fusion Proteins/physiology; Repetitive Sequences, Amino Acid; S Phase; Sequence Deletion; Signal Transduction/genetics/physiology; Stomach Neoplasms/genetics/*pathology; Trans-Activation (Genetics)/drug effects; Transfection; Tumor Stem Cell Assay
AD State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, 15 West Chang-Le Rd., Xi'an, Shaanxi Province, China.
SP englisch
PO USA