OBJECTIVE: To investigate the expression of matrix metalloproteinase-1 (MMP-1), E26 transformation-specific-1 (Ets-1) in laryngeal carcinoma and to discuss their relevance and the roles in carcinogenesis and development of laryngeal carcinoma. METHOD: Immunohistochemical technique was used to detect the expression of MMP-1 and Ets-1 protein in 34 tissues of laryngeal carcinoma and 34 para-carcinoma tissues, 15 cases of vocal cord polyps, and the use of the pathological image analysis software, we analysis the results of immunohistochemical semi-quantitatively. RESULT: (1) The expression of MMP-1 and Ets-1 protein in laryngeal carcinoma tissues is obviously higher than that in para-carcinoma and in vocal cord polyps respectively (P < 0.05). There is no significant difference between the expression of para-carcinoma and vocal cord polyps(P > 0.05). (2) The expression of MMP-1, Ets-1 protein isn't related to patients' age and sex, tumor size,clinical classification (P > 0.05), but related to pathological grade, clinical stage and lymph nodes metastasis (P < 0.05). (3) There is a positive correlation between the expression of MMP-1 and Ets-1 in laryngeal carcinoma. CONCLUSION Overexpression of MMP-1 and Ets-1 was observed in laryngeal carcinoma. The high expression of MMP-1 and Ets-1 may contribute to the carcinogenesis and development of laryngeal carcinoma,which is a important value to judge the malignant degree and progress of laryngeal carcinoma.
Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Female ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 1 ; metabolism ; Middle Aged ; Proto-Oncogene Protein c-ets-1 ; metabolism

Adult ; Humans ; Leukocytes, Mononuclear ; metabolism ; Lupus Erythematosus, Systemic ; genetics ; Proto-Oncogene Protein c-ets-1 ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

Animals ; Arginine Vasopressin ; physiology ; Connective Tissue Growth Factor ; physiology ; Glomerular Mesangium ; pathology ; Humans ; Integrin alpha1beta1 ; physiology ; Kidney Diseases ; etiology ; Proto-Oncogene Protein c-ets-1 ; physiology

OBJECTIVETo investigate effect of AP-1 and Ets binding site adjacent to matrix metalloproteinase-9 (MMP-9) promoter on activation of MMP-9 transcription of nasopharyngeal carcinoma cells transfected with EBV-encoded latent membrane protein 1 (LMP1), and to ascertain if cross-talk between c-Jun and Ets1 is involved in LMP1-regulating expression of MMP-9.

METHODSSite-directed mutagenesis technique was used to establish a series of mutants, including MMP-9-CAT-Ets(-540)mt, MMP-9-CAT-AP-1(-533)mt and MMP-9-CAT-AP-1(-533)/Ets(-540)mt. After the mutants were transfected into LMP1-expressing NPC HNE2 cells regulated by Tet-on system (pTet-on-LMP1 HNE2), CAT activity of these mutants were assayed with induction of LMP1. With blockade of c-Jun or Ets1 antisense oligonucleotides, the activity of MMP-9 induced by LMP1 was assayed with gelatin zymography.

RESULTSThe CAT activity of MMP-9-Ets(-540)mt-CAT, MMP-9-AP-1(-533)mt-CAT, MMP-9-AP-1(-533)/Ets(-540) mt-CAT decreased significantly compared to MMP-9-CAT wt. After blockade with c-Jun or Ets1 antisense oligonucleotides, activity of MMP-9 induced by LMP1 decreased significantly, especially with combined blockade of c-Jun and Ets1.

CONCLUSIONThe results suggest that transcription factor AP-1 and Ets play an crucial role in activation of MMP-9 transcription induced by LMP1, and cross-talk between c-Jun/Ets1 is involved in expression of MMP-9 mediated by LMP1.

Herpesvirus 4, Human ; genetics ; Humans ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Nasopharyngeal Neoplasms ; metabolism ; virology ; Proto-Oncogene Protein c-ets-1 ; genetics ; Proto-Oncogene Proteins c-jun ; genetics ; Transfection ; Tumor Cells, Cultured ; Viral Matrix Proteins ; genetics

OBJECTIVETo elucidate the expression of tanscription factor Ets-1 mediated by EB virus encoded latent membrane protein 1 (LMP1) in nasopharyngeal carcinoma (NPC) cells.

METHODSLMP1-expressing NPC HNE2 cells regulated by Tet-on system (pTet-on-LMP1 HNE2) were used. Expression of LMP1 and Ets-1 was observed after induction with Doxycycline (Dox). Expression of Ets-1 mRNA and protein was detected by RT-PCR and Western blot, respectively. The phosphorylation level of Ets-1 protein was examined by co-immunoprecipitation. The DNA binding activity of Ets-1 was detected by electrophoretic-mobility shift assay (EMSA).

RESULTSAfter induction with Dox in pTet-on-LMP1 HNE2 cells, to some extent, the expression of Ets-1 mRNA and protein, its phosphorylation level and DNA binding activity were increased with enhancement of LMP1 expression.

CONCLUSIONLMP1 induces transcriptional activation and expression of Ets-1 which may contribute to the development of NPC.

Carcinoma, Squamous Cell ; metabolism ; pathology ; virology ; Cell Line, Tumor ; Doxycycline ; pharmacology ; Herpesvirus 4, Human ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; virology ; Phosphorylation ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Proteins ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-ets ; RNA, Messenger ; biosynthesis ; genetics ; Transcription Factors ; biosynthesis ; genetics ; Viral Matrix Proteins ; biosynthesis ; genetics ; physiology

OBJECTIVETo investigate the relationship between the expressions of KAI1, nm23, ETS-1, vascular endothelial growth factor (VEGF) and microvascular density (MVD) and lymph node metastasis and prognosis in nasopharyngeal carcinoma (NPC).

METHODSThe Envision immunohistochemical method was used to detect the expressions of KAI1, nm23, ETS-1 and VEGF in 50 cases of non-keratinizing carcinoma (NKC) with cervical lymph node metastasis, 30 cases of NKC without cervical lymph node metastasis at the primary diagnoses and 30 cases of non-tumor nasopharyngeal tissues (NP). The microvascular density was counted by immunostaining with CD34.

RESULTS(1) The expression rates of KAI1 and nm23 protein in NKC with cervical lymph node metastasis group and without cervical lymph node metastasis group and NP group increased successively , the difference being significant (P < 0.05); The expression rates of ETS-1 and VEGF protein in NKC with cervical lymph node metastasis group and without cervical lymph node metastasis group and NP group increased successively, the difference being significant (P < 0.05). (2) In 80 NKC cases, the MVD was respectively lower in KAI1 and nm23 protein positive groups than those in the negative groups (P < 0.05); the MVD was respectively higher in ETS-1 and VEGF protein positive groups than those in the negative groups (P < 0.05 ). (3) There was significant difference between the MVD, the number of NKC without cervical lymph node metastasis cases in the single expression of KAI1 or nm23 protein and in common expression of KAI1 and nm23 protein (P < 0.05), in the same as between the single expression of ETS-1 or VEGF protein and in common expressions of ETS-1 and VEGF protein (P < 0.05). (4) There was positive correlation between the expressions of KAI1 and nm23 protein (P < 0.01), as well as between the expressions of ETS-1 and VEGF protein (P < 0.01). (5) the 5-year survival rates of the patients correlated with cervical lymph node metastasis and the expressions of KAI1, nm23, ETS-1 and VEGF proteins in NKC (P < 0.05).

CONCLUSIONSThe expressions of KAI1, nm23, ETS-1 and VEGF proteins were highly related to MVD in NPC,cervical lymph node metastasis and prognosis. They might be considered to be reference indicator for evaluating the cervical lymph node metastasis and prognosis of NPC.

Adult ; Aged ; Female ; Humans ; Kangai-1 Protein ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; metabolism ; Nasopharyngeal Neoplasms ; blood supply ; metabolism ; pathology ; Prognosis ; Proto-Oncogene Protein c-ets-1 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

OBJECTIVETo study the expression of VEGF, KDR, MMP-1, and its transcription factor Ets-1 on the interstitial neovasculogenesis in human cervical carcinoma on molecular level, which may provide further theoretic bases on judgement of prognosis and explain interregularity between neovasculagenetic factors.

METHODSVEGF, KDR, MMP-1, and Ets-1 were detected in 87 cervical carcinomas by in situ hybridization and immunohistochemistry. The survival curves for patients with detected tumors were compared with the curves for those without tumors. Multivariate analyses were performed with Pearson analysis.

RESULTSVEGF mRNA and its protein were mainly expressed in cytoplasms of tumor cells, positive rate was 78.6% (68/87) and 70.4% (61/87) respectively. KDR mRNA and its protein were mainly expressed in vascular endothelial cells, as correlation coefficient between KDR and VEGF was 0.892. Over expression of MMP-1 was seen in both endothelial cells and tumor cells, especially in hyperplasia of endothelial cells. Ets-1 was mainly expressed in both endothelial cells and tumor cells, correlation coefficient between Ets-1 and KDR, MMP-1, was 0.900 and 0.873, respectively. Four factors of above were highly related with tumor differentiation, lymph nodes metastasis as well as 5 years survival rate.

CONCLUSIONSVEGF, KDR, MMP-1, and Ets-1 are important factors on neovasculogenesis in cervical carcinoma, which may be considered to be reference indicator for determining biology behavior of cervical carcinoma, and may provide further theoretic bases on antineovasculagenetic therapy.

Adult ; Aged ; Carcinoma, Squamous Cell ; blood supply ; metabolism ; Female ; Humans ; In Situ Hybridization ; Matrix Metalloproteinase 1 ; biosynthesis ; genetics ; Middle Aged ; Neovascularization, Pathologic ; Protein-Tyrosine Kinases ; biosynthesis ; genetics ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Proteins ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-ets ; Receptors, Vascular Endothelial Growth Factor ; biosynthesis ; genetics ; Transcription Factors ; biosynthesis ; genetics ; Uterine Cervical Neoplasms ; blood supply ; metabolism ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

OBJECTIVETo assess the association between 2 single nucleotide polymorphisms (SNPs) of ETS1 gene and susceptibility to systemic lupus erythematosus (SLE) in a northern Chinese Han population.

METHODSTwo SNPs within the ETS1 gene mapped to 11q23 were selected based on HapMap data. Genotyping was conducted with Taqman method in 231 patients with SLE and 474 healthy controls from Qilu Hospital, Shandong and analyzed with PLINK1.07 software. Haplotypes were analyzed with SHEsis software.

RESULTSA statistically significant difference was detected in the distribution of rs1128334 and rs4937333 genotypes between the two groups (all P< 0.01). For rs1128334, the frequency of the minor allele was 0.291 and 0.428 in controls and cases, respectively. For rs4937333, the minor allele frequency was 0.381 and 0.476 in controls and cases respectively. An A-C haplotype was found to be strongly associated with increased risk for SLE, while another haplotype G-C may reduce this risk.

CONCLUSIONOur study has suggested that rs1128334 and rs4937333 are strongly associated with the risk for SLE in northern Chinese Han population.

3' Untranslated Regions ; Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Female ; Genetic Association Studies ; Humans ; Lupus Erythematosus, Systemic ; ethnology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Proto-Oncogene Protein c-ets-1 ; genetics ; Young Adult

OBJECTIVETo investigate the expression of Ets-1 in gastric carcinoma, para-cancerous tissue and metastatic lymph nodes, and to determine the relationship between Ets-1 expression and clinicopathological features, angiogenesis and survival of patients with gastric carcinoma.

METHODSGastric carcinoma tissue microarray was used to determine Ets-1 protein expression by SP immunohistochemical staining in 189 advanced gastric cancer, 54 papacancerous tissues, 41 metastatic lymph nodes and 32 control tissues.

RESULTSThe positive rates for Ets-1 expression of the carcinoma, paracancerous and control tissues were 71.4%, 29.6% and 18.8%, respectively, with a significant difference among the three groups (P < 0.01). In the cancer tissues, the positive rate of Ets-1 protein expression was significantly associated with depth of invasion and lymph node metastasis (P < 0.01), but not associated with degree of differentiation, Lauren's histological type, sex, age, and size of tumor (P > 0.05). The positive rates for Ets-1 expression of the 41 gastric cancer and 41 metastatic lymph nodes were significantly different (P < 0.05). In metastatic lymph nodes, the positive rate for Ets-1 expression was higher. The MVD in Ets-1 positive tumors was higher than that in the Ets-1 negative tumors, with a significant difference (P < 0.05). Kaplan-Meier survival analysis showed that the survival time of Ets-1-negative patients was longer than that of Ets-1-positive patients (P < 0.05). Cox regression analysis showed that Ets-1 expression was not an independent prognostic factor of gastric carcinoma.

CONCLUSIONA higher expression of Ets-1 is involved in carcinogenesis, development, invasion, and metastasis of gastric cancer. Ets-1 plays an important role in angiogenesis in gastric cancer. Ets-1 is a useful marker for predicting the outcome for patients with gastric carcinoma, though it is not an independent prognostic indicator.

Adult ; Aged ; Female ; Humans ; Lymphatic Metastasis ; Male ; Microvessels ; metabolism ; pathology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neovascularization, Pathologic ; metabolism ; pathology ; Paraffin Embedding ; Proportional Hazards Models ; Proto-Oncogene Protein c-ets-1 ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Survival Rate

OBJECTIVETo investigate the effect of simulated microgravity on erythroid differentiation of K562 cells and explore the possible mechanism.

METHODSThe fourth generation rotating cell culture system was used to generate the simulated microgravity environment. Benzidine staining was used to evaluate the cell inhibition rate, and real-time quantitative PCR (qRT-PCR) was used to detect GATA-1, GATA-2, Ets-1, F-actin, β-Tubulin and vimentin mRNA expressions. The changes of cytoskeleton were observed by fluorescence microscopy, and Western blotting was employed to assay F-actin, β-tubulin and vimentin protein expression levels.

RESULTSBenzidine staining showed that simulated microgravity inhibited erythroid differentiation of K562 cells. K562 cells treated with Hemin presented with increased mRNA expression of GATA-1 and reduced GATA-2 and Ets-1 mRNA expressions. Simulated microgravity treatment of the cells resulted in down-regulated GATA-1, F-actin, β-tubulin and vimentin mRNA expressions and up-regulated mRNA expressions of GATA-2 and Ets-1, and reduced F-actin, β-tubulin and vimentin protein expressions. Exposure to simulated microgravity caused decreased fluorescence intensities of cytoskeletal filament F-actin, β-tubulin and vimentin in the cells.

CONCLUSIONSimulated microgravity inhibits erythroid differentiation of K562 cells possibly by causing cytoskeleton damages to result in down-regulation of GATA-1 and up-regulation of GATA-2 and Ets-1 expressions.

Actins ; metabolism ; Cell Differentiation ; Down-Regulation ; GATA1 Transcription Factor ; metabolism ; GATA2 Transcription Factor ; metabolism ; Hemin ; pharmacology ; Humans ; K562 Cells ; Proto-Oncogene Protein c-ets-1 ; metabolism ; Tubulin ; metabolism ; Up-Regulation ; Vimentin ; metabolism ; Weightlessness Simulation