ABSTRACT
Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements or abnormal transcription in many human cancers. Although multiple gastric cancer genomes have been sequenced, the driving recurrent gene fusions have not been well characterized. Here, we used paired-end transcriptome sequencing to identify novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary human gastric cancer tissues and their adjacent normal tissues. Multiple samples revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B-STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion transcript was detected in 21.3% of primary human gastric cancers but not in adjacent matched normal gastric tissues. Based on reverse transcription PCR analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B-STARD3 appears to be generated by RNA processing without chromosomal rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling. Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling.
Subject(s)
Carrier Proteins/genetics , Dopamine and cAMP-Regulated Phosphoprotein 32/genetics , Membrane Proteins/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Animals , Blotting, Western , Carcinogenesis/genetics , Carcinogenesis/metabolism , Cell Line, Tumor , Chromones/pharmacology , Enzyme Inhibitors/pharmacology , Female , Humans , Male , Mice, Nude , Middle Aged , Morpholines/pharmacology , Oncogene Proteins, Fusion/genetics , Phosphoinositide-3 Kinase Inhibitors , Phosphorylation/drug effects , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Transplantation, Heterologous , Tumor Burden/geneticsABSTRACT
To investigate whether tick-borne encephalitis viruses (TBEVs) are present in South Korea, Korean ixodid ticks were tested for TBEV RNA. Ticks (n = 2460) were collected from wild and domestic animals or by flagging at forest and grassland in 12 regions of five provinces in 2005-06. Four species in two genera were identified, yielding 197 sample pools (1-20 ticks per pool); from these, 12 envelope protein gene fragments of TBEV were amplified by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR). Ten of the 2104 adult ticks (0.4%) and two of the 356 nymph ticks (0.2%) were positive for the envelope (E) gene of TBEV. Twelve TBEV RNA-positive samples were detected in Gyeonggi and Gangwon provinces. Phylogenetic analysis showed that the E genes of the TBEV isolates were clustered with the Western European subtype (98% identity). This study suggests that TBEVs may exist in Korea.
Subject(s)
Encephalitis Viruses, Tick-Borne/isolation & purification , Ixodidae/virology , Animals , Encephalitis Viruses, Tick-Borne/genetics , Korea , Nymph/virology , PhylogenyABSTRACT
The anti-free radical effects of water extracts of crude Astragalus mongholicus (CAWE) and honey-fried Astragalus mongholicus (HAWE) have been studied. Both extracts have similar effects in scavenging 0.2 in Xan/Xo system. The effect of CAWE is stronger than that of HAWE in scavenging reactive oxygen species (ROS) produced by PMA and stimulated by PMN and also in scavenging OH engendered by Fentons reaction. This suggests that frying process may decrease the ROS scavenging activities of Astragalus mongholicus.
