Study of a candidate tumor suppressor gene on 9q32, deleted in esophageal cancer 1 (DEC1), in esophageal cancer

Esophageal squamous cell carcinoma (ESCC) is a malignancy, which is the seventh most common fatal cancer worldwide and the second most common cause of cancer-related deaths in Northern China. A novel candidate tumor suppressor gene (TSG), DEC1 (Deleted in Esophageal Cancer 1), has been found located at 9q32 by high frequency of loss of heterozygosity (LOH) by previous investigators. They found that expression of DEC1 was reduced in esophageal carcinoma. The DEC1 cDNA clone is able to suppress cancer cell growth in vitro and tumor growth in vivo in nude mice. Hence, DEC1 is believed to play an important role in tumor suppression in ESCC. Previous studies indicated that DEC1 induced tumor suppression in the SLMT-1 ESCC cell line system; in this project several other aspects of DEC1 were studied. Reverse transcriptase polymerase chain reaction was used to determine the DEC1 expression level in 16 ESCC cell lines and 25 Hong Kong esophageal patient cancer tissues; 100% cell lines and 52% tumors showed reduced DEC1 expression levels. However, there were no clinically significant associations identified related to this down-regulation. Cellular location of DEC1 protein was studied using epitope-tagging and immunofluorescence staining and the protein was detected in both the cytoplasm and nucleus. In vitro cell migration, cell invasion, and soft agar assays were used to determine the impact of DEC1 expression in the stable transfectants. Only the soft agar assay showed statistically significant differences with the vector-alone controls, indicating that DEC1 may be involved in anchorage-independent growth. In addition, the global gene expression affected by DEC1 in stable transfectants was investigated with cDNA oligonucleotide microarrays. Three candidate genes, TFPI-2, GDF15, and DUSP6, were identified and shown to be down-regulated in ESCC cell lines. A DEC1 antibody was also successfully generated and may be useful in future DEC1 protein level studies