OBJECTIVETo study the oncogene transcriptor c-myc, stimulatory protein 1 (SP1) expression in ameloblastoma (AB) and their relation with telomerase reverse transcripase (hTERT), and to investigate the clinical biological characteristics of AB.

METHODSThe expression was observed in AB by in situ hybridization and SP method.

RESULTSThe positive rates of c-myc mRNA, hTERT mRNA and SP1 protein were 81.5% (44/54), 94.4% (51/54) and 83.3% (45/54), respectively. Their positive rates increased as AB recurred and transformed malignantly. A strong correlation was found between hTERT and c-myc, hTERT and SP1 (rs = 0.853, P < 0.001; rs = 0.900, P < 0.001).

CONCLUSIONActivity of telomerase plays an important role in the tumorigenesis development of AB. Increasing of hTERT expression may be related to c-myc and SP1. The expression of these three parameters has a significant correlation with the clinical biological characteristics of AB.

Ameloblastoma ; metabolism ; Humans ; Proto-Oncogene Proteins c-myc ; metabolism ; Sp1 Transcription Factor ; metabolism ; Telomerase ; metabolism

Sp1 is a ubiquitous nuclear factor that plays a key role in maintaining basal transcription of 'house-keeping' genes. It has been demonstrated that Sp1 is involved in many cellular process, e.g.cell growth and differentiation. Sp1 plays an extremely important role in growth and metastasis of many tumors by regulating oncogenes, tumor suppressor genes, cell cycle control molecules, growth-related signal transductions, angiogenesis-related factors, as well as apoptosis. The expression of Sp1 and its activity are strictly regulated. Mechanisms include the modulation of Sp1 and interactions between Sp1 and other molecules. New treatment with Sp1 as the target will bring profound impacts on the strategy of clinical chemotherapy of tumor.
Apoptosis ; genetics ; Humans ; Neoplasm Metastasis ; genetics ; Neoplasms ; genetics ; Sp1 Transcription Factor ; genetics ; metabolism

OBJECTIVETo investigate the expression of transcription factor SP1, vascular endothelial growth factor(VEGF) and CD34 in serosa-infiltrating gastric cancer and their relationship with biological behavior and survival rate.

METHODSImmunohistochemical technique was used to detect the expression of SP1, VEGF and CD34(described by microvessel density, MVD) in 68 specimens with serosa-infiltrating gastric cancer.

RESULTSThe positive expression rates of SP1 and VEGF in serosa-infiltrating gastric cancer were 50.0% and 52.9% respectively. In positive SP1 specimens, the positive rate of VEGF(73.5%) was significantly higher than that of negative SP1 specimens (32.4%, chi(2)=11.57, P=0.01). The mean tumor MVD was correlated with the expression levels of SP1 and VEGF(P<0.01). There was a significant correlation of the SP1 expression with tumor size and growth pattern(P =0.01). The expression levels of VEGF and MVD were correlated with Borrmann types, cell differentiation, metastatic lymph nodes and growth pattern(P<0.01). Univariate analysis revealed that SP1 and VEGF expression, MVD, Borrmann types, lymph node metastasis, tumor size and growth pattern were significant prognostic factors related to survival time. Multivariate analysis showed that SP1 expression, MVD and growth pattern were independently prognostic factors of poor survival.

CONCLUSIONSThe activation of SP1 contributes to angiogenesis and metastasis in gastric cancer through the up-regulation of VEGF. SP1, VEGF and MVD may serve as valuable indicators of biological behavior of gastric cancer. SP1 protein expression is not related with the number of metastatic lymph nodes. SP1 expression and MVD may serve as valuable indicators of prognosis in gastric carcinoma.

Adult ; Aged ; Antigens, CD34 ; metabolism ; Female ; Humans ; Male ; Microcirculation ; Middle Aged ; Prognosis ; Sp1 Transcription Factor ; metabolism ; Stomach Neoplasms ; blood supply ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVE: To study the transcriptional regulation of SP1 on the scaffold protein ARRB1 and its influence on the progression of T-cell acute lymphoblastic leukemia (T-ALL). METHODS: pGL3-ARRB1-luc, pCDNA3.1-SP1 and other transcription factor plasmids that might be combined were constructed, and the binding of transcription factors to the promoter of ARRB1 was identified by dual luciferase reporter gene assay. Stable cell lines with over-expressed SP1 (JK-SP1) was constructed by lentiviral transfection, and the expression correlation of SP1 with ARRB1 was demonstrated by RT-PCR and Western blot. Further, the apoptosis, cell cycle and reactive oxygen species (ROS) were detected by flow cytometry. The effect of SP1 on propagation of leukemic cells was observed on NCG leukemic mice. RESULTS: The expression of fluorescein were enhanced by co-transfection with pCDNA3.1-SP1 and pGL3-ARRB1-luc plasmids in HEK293T cell line (P<0.001), meanwhile, compared with the control group, the expression of ARRB1 mRNA and protein were increased in JK-SP1 cells (both P<0.01). Further in vitro experiments showed that, compared with the control group, the apoptosis rate was higher (x=22.78%) , the cell cycle was mostly blocked in G₁ phase (63.00%), and the content of reactive oxygen species increased in JK-SP1 cells. And in vivo experiments showed that the mice injected with JK-SP1 cells through tail vein had a favorable overall survival time (average 33.8 days), less infiltration in liver and spleen tissue. CONCLUSION Transcription factor SP1 promotes the transcription and expression of ARRB1 by binding the the promoter of ARRB1 directly, thus delays the progress of T-ALL in vitro and in vivo. The study improves the pathogenesis of ARRB1 regulating the initiation and development of T-ALL, and provides theoretical basis for the development of new possible targeted drugs.
Humans ; Animals ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; HEK293 Cells ; Reactive Oxygen Species ; Transcription Factors ; T-Lymphocytes ; Cell Line, Tumor ; Sp1 Transcription Factor/metabolism*

Nicotinamide at millimolar concentrations affects cell survival in various conditions, and is being utilized therapeutically in many human diseases. However, the effect of an acute treatment of nicotinamide at such high dose on gene expression and cellular metabolism has rarely been determined previously. In this study, we found that levels of O-N-acetylglucosamin(O- GlcNAc)ylated proteins including Sp1 acutely decreased upon treatment of 10 mM nicotinamide. Concomitantly, Sp1 protein level decreased rapidly through accelerated proteasome-mediated proteolysis. Cotreatment of glucosamine or 2-deoxyglucose, which inhibits protein deGlcNAcylation, effectively blocked the decrease induced by nicotinamide. Interestingly, the decline in the levels of Sp1 and protein O- GlcNAcylation was only transient lasting for two days post treatment, and this pattern matched closely the rapid fluctuation of the cellular [NAD(+)]. Our results suggest a possible link between cellular nicotinamide metabolism and protein O-GlcNAcylation, and an existence of cellular [NAD(+)] homeostasis.
Acetylglucosamine/*metabolism ; Blotting, Western ; Dose-Response Relationship, Drug ; Down-Regulation/*drug effects ; Humans ; Hydrolysis ; Niacinamide/*pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Sp1 Transcription Factor/metabolism

We studied the function and mechanism of miR-24 in regulating beta-like globin gene expression. We first detected the expression of miR-24 during erythroid differentiation and also detected the globin gene expression in miR-24 overexpressing K562 cells through q-PCR. Dual-luciferase reporter assay and Western blotting were used to identify target genes of miR-24. "Rescue experiment" was further used to investigate the regulation of miR-24 on globin gene expression whether depending on targeting Sp1 or not. We found that miR-24 increased during hemin-induced K562 cells and EPO-induced HPCs (hematopoietic progenitor cells) erythroid differentiation. Overexpression of miR-24 in K562 cells promoted the epsilon- and gamma-globin gene expression during hemin-induced erythroid differentiation through targeting the negative globin regulator Sp1. These results suggested that miR-24 can improve the expression of beta-like globin gene through targeting Sp1.
Cell Differentiation ; Gene Expression Regulation ; Hematopoietic Stem Cells ; metabolism ; Humans ; K562 Cells ; MicroRNAs ; genetics ; Sp1 Transcription Factor ; genetics ; epsilon-Globins ; genetics ; gamma-Globins ; genetics

OBJECTIVETo observe the expression of hepatocyte growth factor (HGF), transcription factor SP1, vascular endothelial growth factor (VEGF) and CD34 (demonstrating by microvessel density, MVD) in serosa-infiltrative gastric cancer (T3) and their relations with the pathobiological behavior of the tumor, and to investigate the molecular basis of the defluxion of gastric cancer cells in abdominal cavity and its influence on prognosis.

METHODSSelective collection of peritoneal lavage was obtained from 80 patients with serosa-infiltrative gastric cancer received operation from April to December in 2007. The cancer cells were detected by using peritoneal lavage cytology (PLC) and immunochemistry of cytokeratin 18 (CK18). Immunohistochemistry was applied to detect the HGF, SP1, VEGF and CD34 in serosa-infiltrative gastric cancer tissues. The rigorous follow-up was carried out for the patients.

RESULTSThe positive rate of PLC was 63.8% (51/80), and the positive rate of immunochemistry of CK18 was 75.0% (60/80). The positive cases in PLC were positive in immunochemistry of CK18 also, while 9 negative cases in PLC were positive with CK18, and of them 6 cases were determined positive with exfoliated cancer cells through pathological consulting. So the positive rate of exfoliated cells of this group was 71.3% (57/80). The positive rates of HGF, SP1 and VEGF in gastric cancer tissues were 57.5%, 52.5% and 55.0%, respectively, and were all significantly correlated with the MVD (P < 0.05). HGF, SP1, VEGF and MVD were correlated with the positive rate of exfoliated cells (P < 0.05). HGF, SP1, VEGF and MVD were found significantly related to prognosis on univariate analysis (P < 0.05), and it was demonstrated that HGF, SP1 and VEGF were independent prognostic influential factors on Logistic regression analysis (P < 0.05).

CONCLUSIONSThe expression of HGF, SP1, VEGF and MVD are related with the biological behaviour of serosa-infiltrative gastric cancer. The detection of these factors might be helpful in predicting the defluxion of gastric cancer cells and postoperative recurrence.

Antigens, CD34 ; metabolism ; Female ; Follow-Up Studies ; Hepatocyte Growth Factor ; metabolism ; Humans ; Male ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; Peritoneal Lavage ; Prognosis ; Serous Membrane ; pathology ; Sp1 Transcription Factor ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism

Cells, Cultured ; Flutamide ; pharmacology ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Proto-Oncogene Proteins c-myb ; metabolism ; Sp1 Transcription Factor ; metabolism ; Testosterone ; antagonists & inhibitors ; physiology ; Transcription Factors ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo evaluate the effects of Bevacizumab on the tumor growth, proliferation and apoptosis of gastric cancer xenograft, and the impacts on the VEGF and Sp1 expression.

METHODSGastric cancer xenografts in nude mice were established using SGC-7901 gastric cancer cell line. The nude mice were randomly divided into two groups, Bevacizumab treatment group and PBS group. The tumor sizes were measured for tumor growth curve. The proliferation and angiogenesis were evaluated by immunohistochemistry (IHC) staining of Ki67 and CD34. TUNEL assay was used for apoptosis evaluation. The expression of VEGF and Sp1 in tumor cells were detected by IHC and Western blot.

RESULTSCompared to the PBS group, the tumor growth decreased significantly (P<0.05), the proliferation of tumor cells and angiogenesis decreased, and apoptosis index increased significantly [(5.3 ± 1.8)% vs. (16.7 ± 6.7)%, P<0.01] in Bevacizumab group. The results of IHC and Western blot demonstrated that the expression of VEGF and the microvessel density (MVD) was decreased (4.0 ± 1.0 vs. 16.3 ± 1.5, P<0.001) in Bevacizumab treatment group. No obvious changes of Sp1 expression were observed in Bevacizumab treatment group.

CONCLUSIONSBevacizumab can inhibit the growth of gastric cancer xenografts in nude mice, decrease the VEGF expression and MVD. However, the compensatory up-regulation of transcription factor Sp1 is not affected by Bevacizumab.

Animals ; Antibodies, Monoclonal, Humanized ; pharmacology ; Apoptosis ; Bevacizumab ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Mice ; Mice, Nude ; Sp1 Transcription Factor ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVETo determine the expression patterns of metastasis associated 1 family member 2 (MTA2) in gastric cancer and non-cancerous gastric mucosa, and analyze its relationship with nuclear transcription factor Sp1 expression.

METHODSTissue samples and clinicopathological information from 83 gastric cancer patients, who underwent surgery, were collected from Shanghai Rui Jin Hospital. All samples included cancer tissue and non-cancerous mucosa which was 5 cm away from the tumor lesion. The expression of MTA2 and Sp1 were detected by immunohistochemistry (IHC) staining. The mRNA of MTA2 was also detected by reverse transcription-polymerase chain reaction (RT-PCR). SPSS software was used for statistical analysis.

RESULTSThe expression of MTA2 protein was significantly higher in primary lesions of the gastric cancer than that in non-cancerous mucosa by IHC (31.3% vs 12.0%, P < 0.01). MTA2 expression was closely related with tumor invasion or T staging (χ(2) = 5.677, P < 0.05). Yet, no significant relationship was observed between MTA2 expression and other clinicopathological parameters, including the age, sex, tumor differentiation, Lauren classification, lymph node metastasis, distant metastasis, as well as pathological staging. Furthermore, MTA2 expression was concomitant with Sp1 expression (r = 0.320, P < 0.05). Elevated MTA2 expression was observed in Sp1 positive cancer tissues (χ(2) = 9.565, P < 0.01). RT-PCR results also demonstrated that MTA2 mRNA was also highly expressed in the tissue samples with Sp1 expression.

CONCLUSIONSMTA2 is highly expressed in the primary lesions of gastric cancer than that in adjacent non-cancerous tissues, and is closely related with tumor invasion. MTA2 expression is elevated in Sp1 positive gastric cancer.

Female ; Gene Expression Regulation, Neoplastic ; Histone Deacetylases ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Sp1 Transcription Factor ; metabolism ; Stomach Neoplasms ; metabolism ; pathology