Gene Function And Transcriptional Regulation Studies Of A Novel Esophageal Cancer Related Gene 1 (ECRG1)

Esophageal cancer related gene 1 (ECRGl) is a novel candidate of tumor suppressor gene identified in our laboratory. Previous studies have shown that the expression of ECRGl is gradually down-regulated from normal esophageal epithelium, adjacent tissue to esophageal cancer. The in vitro and in vivo assays also indicated that overexpression of ECRGl protein inhibits tumor cell proliferation. Thus, ECRGl may play an important role in the development of esophageal squamous cell carcinoma (ESCC). In this thesis, deep studies have focused on ECRGl functions on the levels of genome, transcription and protein. 1. Genomic alterations on the coding region of ECRGl geneOn the genomic levels, we screened mutations and SNPs in the coding region of ECRGl and found three SNPs, which are located in exon 3, 8, and 9, respectively. Particularly, the Arg290Gln SNP in exon 8 located in the Asp conserved region of ECRGl serine protease catalytic domain, might be associated with increased risk of ESCC. A case-control study was carried out among Chinese population for this polymorphism. Our results indicate that the ECRGl 290Gln variant allele might be a genetic susceptibility factor for developing ESCC, especially in the smoking population. Loss of heterozygosity (LOH) was also assessed with two of new polymorphisms in 80 DNA samples of tumors and normal tissues adjacent to the tumors in Linxian. The results showed that the rate of LOH was 23% in ECRGl coding region suggesting that LOH might be one of the reasons resulting in ECRGl genomic instability.