Expression of early growth response-1 in colorectal cancer and its relation to tumor cell proliferation and apoptosis

Abstract

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 non‑metastatic 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.

CDK6 as a key regulator of hematopoietic and leukemic stem cell activation

“…Egr1 is expressed at high levels in transformed differentiated cells and functions as a proto-oncogene in certain tumor types. [33][34][35] Consistently, we find high levels of Cdk6 mRNA paralleled by a statistically significant upregulation of Egr1 in transformed BCR-ABL p1851 cells (supplemental Figure 6A). Chromatin immunoprecipitation (ChIP) analysis revealed the presence of CDK6 at the Egr1 promoter at levels comparable to its binding to the p16…”

Repression of phosphoinositide-dependent protein kinase 1 expression by ciglitazone via Egr-1 represents a new approach for inhibition of lung cancer cell growth

“…Loss of Egr-1 expression has been associated with invasion and anti-apoptotic events, whereas overexpression of Egr-1 suppressed the tumorigenicity and metastatic potential in several cancer cells including lung [34,35]. However, opposite role of Egr-1 were also found in several studies [36,37]. Thus Egr-1 is considered to play dual roles depending on the cell types and environment.…”

Early Growth Response 1-Dependent Downregulation of Matrix Metalloproteinase 9 and Mouse Double Minute 2 Attenuates Head and Neck Squamous Cell Carcinoma Metastasis

“…However, in metastatic tumors, nuclear EGR1 expression was significantly higher in primary tumors compared with that in paired metastatic lymph node tumors. Previous study showed that, in colorectal cancers, EGR1 protein expression was higher in the cytoplasm of metastatic lymph node tissues when compared to that in non-metastatic lymph node tissues [21]. It has already been shown that the effects of nuclear EGR1 and cytoplasmic EGR1 on cancer progression are incompatible [22].…”