title: Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS.
abstract: The function of cellular prion protein (PrP(C)), the essential protein for the pathogenesis and transmission of prion diseases, is still largely unknown. The putative roles of PrP(C) are thought to be related to cell signaling, survival, and differentiation. In a previous study, we showed that PrP(C) was overexpressed in gastric cancer tissues. In the present report, we show that ectopic expression of PrP(C) 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 PrP(C) at both mRNA and protein levels. PI3K/Akt pathway mediated above PrP(C) signal since PrP(C) 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 PrP(C). 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 PrP(C) 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.
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, 15 West Chang-Le Rd., Xi'an, Shaanxi Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.forename: Yanglin
authors.initials: Y
authors.lastname: Pan
authors.forename: Dexin
authors.initials: D
authors.lastname: Zhang
authors.forename: Changcun
authors.initials: C
authors.lastname: Guo
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.forename: Jingbo
authors.initials: J
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Xuegang
authors.initials: X
authors.lastname: Guo
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Taidong
authors.initials: T
authors.lastname: Qiao
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002867:Chromones / Q000494:pharmacology; D056741:Cyclin D; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009025:Morpholines / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D018621:PrPC Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020449:Repetitive Sequences, Amino Acid; D016196:S Phase; D017384:Sequence Deletion; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014410:Tumor Stem Cell Assay
chemical_list: D002867:Chromones; D056741:Cyclin D; D016213:Cyclins; D009025:Morpholines; D009363:Neoplasm Proteins; D018621:PrPC Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt