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1.
Int J Mol Med ; 37(4): 1039-48, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26936013

ABSTRACT

Liver kinase B1 (LKB1) is known to suppress the proliferation, energy metabolism and mesenchymal transition of various cancer cells, and is involved in the regulation of Hippo-Yes-associated protein (Yap) and the Wnt/ß-catenin signaling pathways. However, the role of LKB1 in gastric cancer (GC) was not fully understood. Thus, in the present study, we studied LKB1 and found that protein expression (0.37±0.061 vs. 0.59±0.108, P=0.006) and the protein ratio of p-Yap/Yap (0.179±0.085 vs. 0.8±0.126, P=0.001) were reduced in 54 gastric adenocarcinoma (GAC) tissues compared with the matched adjacent non-cancerous tissues, using western blotting and RT-qPCR assays. LKB1 expression was also observed decreased in 109 GAC tissues compared with 54 adjacent non-cancerous tissues (χ2=4.678, P=0.0306), and negatively correlated with the nuclear expression of Yap (r=-0.6997) and ß-catenin (r=-0.3510), using immunohistochemical analysis. In GC patients, LKB1 expression was negatively associated with tumor size, tumor infiltration, lymph node metastasis and the TNM stage. LKB1 expression was determined to be positively correlated with longer overall survival of GC patients using Kaplan-Meier analysis (P=0.001). Subsequently, LKB1 expression in human GAC AGS cells was enhanced with a full­length LKB1 transfection. In vitro and in vivo proliferation was inhibited in LKB1-overexpressing GC cells compared with the control cells. Yap and ß-catenin expression were assessed by western blotting and RT-qPCR, and were found to be increased in the cytoplasm but decreased in the nucleus in LKB1-overexpressing GC cells compared with the control cells. The increase in cytoplasmic ß-catenin was reversed by the silencing of LKB1 or Yap with shRNAs in LKB1-overexpressing GC cells. Moreover, Yap and ß-catenin mRNA were barely altered by LKB1 overexpression. Thus, we concluded that LKB1 expression was reduced in GAC tissues but that it correlated positively with better prognosis for GC patients. LKB1 inhibits the proliferation of GC cells by suppressing the nuclear translocation of Yap and ß-catenin.


Subject(s)
Adenocarcinoma/metabolism , Nuclear Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Stomach Neoplasms/metabolism , Stomach/pathology , Transcription Factors/metabolism , beta Catenin/metabolism , AMP-Activated Protein Kinase Kinases , Active Transport, Cell Nucleus , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Animals , Cell Cycle Proteins , Cell Line, Tumor , Cell Proliferation , Gastric Mucosa/metabolism , Humans , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Nuclear Proteins/analysis , Protein Serine-Threonine Kinases/analysis , Stomach Neoplasms/pathology , Transcription Factors/analysis , Wnt Signaling Pathway , beta Catenin/analysis
2.
Hepatogastroenterology ; 61(134): 1822-9, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25436386

ABSTRACT

BACKGROUND/AIMS: Zinc finger protein 139 (ZNF139) gene is proved play an important role in gastric cancer. Aim of this study is to identify changes of proteins after ZNF139 gene was inhibited in gastric cancer cell line BGC823. METHODS: siRNA-specific ZNF139 was synthesized and transfected into BGC823; 2-D fluorescence difference gel electrophoresis (2-D DIGE) and liquid chromatography-mass spectrometry (LC-MS) were applied to screen, identify differentially expressed proteins, and function of these proteins was analyzed; Western blot method was applied to verify the identified proteins. RESULTS: ZNF139 expression in siRNA transfected cancer cell BGC823 decreased significantly. Results of 2-D DIGE showed eight differential protein spots, of which seven were identified with LC-MS, including switches associated protein 70, far upstream element binding protein 1, heat shock protein 60, annexin A7, small ubiquitin-like modifier 1 activating enzyme, chaperonin-containing tail-less complex protein 1 and annexin A2. These proteins were found to be associated with proliferation, apoptosis, invasion, metastasis, adhesion of gastric cancer cells with bioinformatic analysis. Western blot analysis confirmed that expressions of these proteins in BGC823 were consistent with the proteomic results. CONCLUSIONS: ZNF139 gene may influence the biological behavior of gastric cancer cells in many ways by regulating multiple proteins.


Subject(s)
Kruppel-Like Transcription Factors/metabolism , Proteomics , RNA Interference , RNA, Small Interfering/metabolism , Stomach Neoplasms/metabolism , Blotting, Western , Cell Line, Tumor , Chromatography, Liquid , Electrophoresis, Gel, Two-Dimensional , Gene Expression Regulation, Neoplastic , Humans , Kruppel-Like Transcription Factors/genetics , Proteomics/methods , RNA, Small Interfering/genetics , Spectrometry, Mass, Electrospray Ionization , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Tandem Mass Spectrometry , Transfection
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