1958

EGR1

early growth response 1;EGR1;early growth response 1

EGR-1|early growth response protein 1|nerve growth factor-induced protein A|transcription factor ETR103|transcription factor Zif268|zinc finger protein 225|zinc finger protein Krox-24

5q31.1

protein-coding

BACKGROUND: Hypoxia up-regulated expression of tissue factor (TF) may facilitate tumor cell metastasis, but transcriptional mechanisms remain undefined. MATERIAL AND METHODS: To verify the role of Egr-1 in hypoxia-induced TF expression in breast cancer cells, quantitative PCR and Western blot analysis were performed. The secretion of VEGF under hypoxia was detected by enzyme-linked immunosorbent assay (ELISA). Egr-1 and HIF-1alpha siRNA were transiently transfected into breast cancer cells to evaluate their specific roles. RESULTS: The increased Egr-1 expression occurring in hypoxic breast cancer cells can up-regulate TF expression and stimulating protein 1(Sp1) was not responsible for the hypoxia-induced expression of TF. HIF-1alpha mediated the hypoxia-induced up-regulation of TF expression through vascular endothelial growth factor (VEGF). The regulatory effects of Egr-1 on TF under hypoxia were independent of HIF-1alpha. Either Egr-1 or HIF-1alpha was responsible for hypoxic induction of tumor cells adhesion. HIF-1alpha, but not Egr-1, had a pivotal role in human breast cancer cells invasion. Both Egr-1 and HIF-1alpha were critical to angiogenesis induced by hypoxic conditions in MDA-MB-231 and HUVEC co-cultures. In nude mice, both Egr-1 and HIF-1alpha small interfering RNA (siRNA) could decrease extravasation of MDA-MB-435 cells in the lung after tail vein injection. CONCLUSIONS: Hypoxia-induced expression of TF in human breast cancer cells depends on Egr-1 and HIF-1alpha, and both of these proteins may play an important role in breast cancer metastasis, either directly or indirectly through the TF pathway.

Early growth response-1 (Egr-1) is implicated in the regulation of cell growth, proliferation, differentiation and apoptosis. Egr-1 is considered tobe either a tumor-suppressor or tumor-promoter, depending on the cell type and environment. The aim of the present study was to evaluate the expression of Egr-1 in colorectal cancer and its correlation with tumor cell proliferation, apoptosis and clinicopathological features. The expression of Egr-1 in colorectal cancer tissues was investigated by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunohistochemistry. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), and cellular proliferative activity was evaluated by immunohistochemical staining with the Ki-67 antibody. Egr-1 expression was significantly elevated in colorectal cancer tissues, when compared to that in the paired normal mucosa at the mRNA and protein levels. In addition, Egr-1 expression was significantly increased in the metastatic lymph node tissues, when compared to that in the nonmetastatic lymph node tissues at the protein level. The mean Ki-67 labeling index (KI) and apoptotic index (AI) values for 158 tumors were 53.6+/-15.4 and 9.0+/-1.0, respectively. Higher KI values were significantly associated with distant metastasis. Lower AI values were significantly associated with lymph node metastasis. However, KI or AI values were not associated with patient survival. The mean KI value of Egr-1-positive tumors was significantly higher than that of Egr-1-negative tumors. However, there was no significant difference between Egr-1 expression and AI value. Positive expression of Egr-1 was significantly associated with age, lymphovascular invasion, lymph node and distant metastasis, tumor stage and poor survival. These results indicate that Egr-1 may be associated with colorectal cancer progression via tumor cell proliferation.

BACKGROUND: To investigate the potential role of a nuclear transcription factor, early growth response-1 (Egr-1), in formation and progression of gastric cancer, we compared its expression in gastric cancers with that in non-cancerous tissues. MATERIALS AND METHODS: Egr-1 mRNA expression was measured using TaqMan RT-PCR. The corresponding protein expression was examined immunohistochemically. RESULTS: Egr-1 mRNA expression was significantly higher in gastric cancer tissues than in normal mucosa (p < 0.0005). These differences were also reflected by protein product expression. Moreover, Egr-1 mRNA expression was higher in cases with metastasis to lymph nodes or remote organs. In cultured gastric cancer cells known to have a high metastatic potential, expression of this mRNA was higher than that of parental cells. CONCLUSION: It was suggested that Egr-1 has a significant role in carcinogenesis and in cancer progression, especially metastasis. Measurement of this mRNA should be useful for evaluation of the metastatic potential of gastric cancer.

Given that previous studies indicated that early growth response 1 (EGR1) exerts pro-tumorigenic effects through regulating heparanase (HPA) transcription, it was hypothesized that EGR1 may correlate with the progression of gastric cancer. One hundred and fifteen patients with gastric cancer were evaluated for the protein and transcript expression of EGR1 and HPA on immunohistochemistry and real-time quantitative polymerase chain reaction (PCR). In normal gastric mucosa, EGR1 protein expression was absent or weak, whereas gastric cancer was positive for EGR1. Seventy gastric cancer patients (60.9%) were positive for cytoplasmic EGR1 expression, and 26 (22.6%) had nuclear expression of EGR1. In the gastric cancer examined, the transcripts of EGR1 were enhanced compared to that of normal gastric mucosa, and positively correlated with EGR1 protein expression. The cytoplasmic or nuclear expression of EGR1 and its transcripts in gastric cancer was positively correlated with tumor infiltration (P < 0.05), lymph node and distant metastasis (P < 0.05), tumor node metastasis (TNM) stages (P < 0.05), but not with age, gender, tumor location and size, histological types or differentiation. Moreover, the protein and transcript expression of EGR1 was correlated with that of HPA in gastric cancer. These results indicate that aberrant expression of EGR1 in gastric cancer is associated with tumor invasion and metastasis, and HPA transcription.

The receptor for advanced glycation end products (RAGE), a pattern recognition receptor that binds multiple ligands derived from a damaged cell environment, contributes to multiple pathologies including cancer. Early growth response 1 (EGR1) is a tumor suppressor gene or a tumor promoter involved in tumorigenesis and progression of some cancers. However, there is some lack of knowledge about the expression and clinical significance of RAGE and EGR1 in human primary gastric adenocarcinoma (GAC). The present study was aimed to investigate the expression and clinical significance of RAGE and EGR1 in human GAC. One hundred and twenty cases of GAC tissues, adjacent non-cancer tissues (ANCT) and metastatic lymph node (MLN) tissues were collected. The expression of RAGE and EGR1 was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were analyzed. As a result, the expression of RAGE in GAC and MLN tissues showed the positive staining mainly in the cytoplasm, with lower reactivity rate compared with the ANCT (P less than 0.001), while EGR1 expression had no significant difference between GAC, MLN tissues and ANCT (P=0.565). Moreover, the positive expression of RAGE was closely associated with the N stage of GAC patients, but did not correlate with their age, gender, tumor size, tumor sites, T stage, and metastatic lymph node (each P>0.05). In addition, Spearman Rank correlation analysis showed the positive correlation of RAGE expression with EGR1 in GAC tissues (r=0.658). Taken together, the expression of RAGE is decreased in GAC and MLN tissues, and is associated with the N stage of GAC patients, suggesting that RAGE may represent a potential therapeutic target for the treatment of GAC.