Biomaterial Database

Expression of TRF1, TRF2, TIN2, TERT, KU70, and BRCA1 proteins is associated with telomere shortening and may contribute to multistage carcinogenesis of gastric cancer. 2010

Hua Hu, and Yang Zhang, and Mei Zou, and Shuai Yang, and Xiao-Qiu Liang

Cancer Research Institute, The Second Affiliated Hospital, University of South China, 421001, Hengyang, Hunan, People's Republic of China.

OBJECTIVE Telomere dysfunction is believed to be a significant factor in carcinogenesis. To elucidate the carcinogenesis mechanism in gastric cancer, the expression of telomeric proteins and changes in telomere length were investigated during multistage carcinogenesis of gastric cancer. METHODS Tissue samples were obtained during surgical operations from the normal gastric mucosa of 10 patients, the precancerous lesions of 15 patients, the gastric cancer tissues (GC) of 20 patients, and of tumors due to gastric cancer with lymph node metastasis (GCLM) from 5 patients. The expression of TRF1, TRF2, and TIN2 proteins was measured by Western blotting, while the expression of TERT, KU70, and BRCA1 proteins was detected using the immunohistochemical method. The mean telomere length was determined by Southern blotting. RESULTS Compared with normal gastric mucosa tissues, the expression of TRF1, TRF2, and TIN2 proteins was significantly higher in precancerous lesions, GC, and GCLM (P < 0.01). The expression of TRF1, TRF2, and TIN2 proteins was significantly higher in GC and GCLM than in precancerous lesions (P < 0.01). The expression of TERT and Ku70 proteins in precancerous lesions and GC tissues was significantly higher than that in normal gastric mucosa tissues (P < 0.01). The expression of TERT and Ku70 proteins in GC tissues was significantly higher than in precancerous lesions (P < 0.01). In normal gastric mucosa, the BRCA1 protein was primarily located in the cell nucleus. In precancerous lesions and GC, the expression of the BRCA1 protein was apparent in the cell cytoplasm. The mean telomere length in precancerous lesions, GC, and GCLM was significantly shorter than that in normal gastric mucosa tissues (P < 0.05). The mean telomere length in GC and GCLM was significantly shorter than that in precancerous lesions (P < 0.05). The mean telomere length in all tissue samples was inversely correlated with the level of TRF1, TRF2, TIN2, TERT, and Ku70 proteins. CONCLUSIONS Our results suggest that the over-expression of telomeric proteins, TRF1, TRF2, TIN2, TERT, and Ku70, and the transposition of the BRCA1 protein may work together to reduce the telomere length in precancerous lesions and gastric cancer, and could contribute to the multistage carcinogenesis of gastric cancer. These findings offer new insight into the mechanism of carcinogenesis in gastric cancer.

UI	MeSH Term	Description	Entries
D007150	Immunohistochemistry	Histochemical localization of immunoreactive substances using labeled antibodies as reagents.	Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D009367	Neoplasm Staging	Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.	Cancer Staging,Staging, Neoplasm,Tumor Staging,TNM Classification,TNM Staging,TNM Staging System,Classification, TNM,Classifications, TNM,Staging System, TNM,Staging Systems, TNM,Staging, Cancer,Staging, TNM,Staging, Tumor,System, TNM Staging,Systems, TNM Staging,TNM Classifications,TNM Staging Systems
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072200	Ku Autoantigen	An ATP-dependent DNA HELICASE that preferentially binds SINGLE-STRANDED DNA. It is a heterodimer consisting of an 80 kDa subunit (XRCC5) and 70 kDa subunit (XRCC6) that functions with DNA LIGASE IV in the repair of DOUBLE-STRANDED DNA BREAKS and V(D)J RECOMBINATION.	G22P1 Antigen,Ku Antigen,Ku Autoantigen, 70 kDa,Ku Autoantigen, 80 kDa,Ku Heterodimer,Ku Protein,Ku70 Antigen,Ku80 Antigen,X-ray Repair Cross-Complementing Protein 5,X-ray Repair Cross-Complementing Protein 6,XRCC5 Protein,XRCC6 Protein,Antigen, G22P1,Antigen, Ku,Antigen, Ku70,Antigen, Ku80,Autoantigen, Ku,Heterodimer, Ku,X ray Repair Cross Complementing Protein 5,X ray Repair Cross Complementing Protein 6
D013274	Stomach Neoplasms	Tumors or cancer of the STOMACH.	Cancer of Stomach,Gastric Cancer,Gastric Neoplasms,Stomach Cancer,Cancer of the Stomach,Gastric Cancer, Familial Diffuse,Neoplasms, Gastric,Neoplasms, Stomach,Cancer, Gastric,Cancer, Stomach,Cancers, Gastric,Cancers, Stomach,Gastric Cancers,Gastric Neoplasm,Neoplasm, Gastric,Neoplasm, Stomach,Stomach Cancers,Stomach Neoplasm
D015153	Blotting, Western	Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.	Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D016615	Telomere	A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.	Telomeres
D019098	Telomerase	An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.	Telomerase Catalytic Subunit,Telomerase Reverse Transcriptase,Telomerase Reverse Transcriptase Catalytic Subunit,Catalytic Subunit, Telomerase,Reverse Transcriptase, Telomerase,Subunit, Telomerase Catalytic,Transcriptase, Telomerase Reverse
D019313	BRCA1 Protein	The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). It contains an N-terminal RING FINGER DOMAIN and is a PROTEIN PHOSPHATASE 1 regulatory subunit. In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)	BRCA1 Gene Product,Breast Cancer 1 Gene Product,Breast Cancer 1 Protein,Breast Cancer Type 1 Susceptibility Protein,Ring Finger Protein 53