Expression of Egr-1 gene and its correlation with the oncogene proteins in non-irradiated and irradiated esophageal squamous cell carcinoma

We study the expression of early growth response gene-1 (Egr-1 gene) in non-irradiated and irradiated human esophageal cancer tissues, and its relationship with the expression of C-fos, C-jun onco-proteins as well as Egr-1 target gene proteins P53, Rb and Bax expression. In situ hybridization (ISH) and immunohistochemistry (IHC) were used respectively to detect Egr-1 mRNA, Egr-1, C-fos, C-jun, P53, Rb and Bax proteins in 80 surgically resected non-irradiated and irradiated tumor specimens of esophageal squamous cell carcinoma. Egr-1 gene mRNA and Bax protein were located in the cytoplasm, whereas Egr-1, C-fos, C-jun, P53, Rb proteins were located in the nuclei. Egr-1 was expressed in nine out of 40 cases (22.5%) of non-irradiated and 23 of 40 cases (57.5%) of irradiated tumor specimens. No correlation was found between Egr-1 gene expression and C-fos, C-jun onco-proteins expression, neither was any correlation disclosed between Egr-1 gene expression with its target gene protein expression. Patients who underwent radiotherapy with Egr-1 overexpressed in their cancer tissue had better prognosis. Radiotherapy up-regulates Egr-1 expression in esophageal carcinoma. Egr-1 overexpression may be a potential radiation response gene marker and may play an important role in prognosis of esophageal squamous cell carcinoma.     

Zinc finger point mutations within the WT1 gene in Wilms tumor patients.

A proposed Wilms tumor gene, WT1, which encodes a zinc finger protein, has previously been isolated from human chromosome 11p13. Chemical mismatch cleavage analysis was used to identify point mutations in the zinc finger region of this gene in a series of 32 Wilms tumors. Two exonic single base changes were detected. In zinc finger 3 of a bilateral Wilms tumor patient, a constitutional de novo C----T base change was found changing an arginine to a stop codon. One tumor from this patient showed allele loss leading to 11p hemizygosity of the abnormal allele. In zinc finger 2 of a sporadic Wilms tumor patient, a C----T base change resulted in an arginine to cysteine amino acid change. To our knowledge, a WT1 gene missense mutation has not been detected previously in a Wilms tumor. By comparison with a recent NMR and x-ray crystallographic analysis of an analogous zinc finger gene, early growth response gene 1 (EGR1), this amino acid change in WT1 occurs at a residue predicted to be critical for DNA binding capacity and site specificity. The detection of one nonsense point mutation and one missense WT1 gene point mutation adds to the accumulating evidence implicating this gene in a proportion of Wilms tumor patients.