Functional investigation of tumor suppressive role of chromosome 9 in esophageal squamous cell carcinoma

Abstract

Background: Esophageal carcinoma (EC) is a very deadly disease, but its molecular basis for tumorigenesis is still largely unknown. The microcell chromosome transfer technique is useful to functionally validate the presence of tumor suppressor genes (TSGs). Early studies indicate there might be important TSGs for EC on chromosome 9. Our study found the LOH frequency of chromosome 9 was very high and three commonly deleted regions were observed at 9p23 –22, 9q13 –22.3, and 9q34 , which suggest the probable locations of TSGs on chromosome 9 involved in esophageal tumorigenesis. Methods: Transfer of chromosome 9 into the highly tumorigenic EC cell line, SLMT-1S1, was accomplished by the method of microcell-mediated chromosome transfer (MMCT). Hybrid cells and their corresponding tumor segregants were studied for the ability to form tumors in a nude mouse model and 33 microsatellite markers were used to detect critical regions associated with their tumor suppression. Results: Comparison of the tumor suppressive hybrid cell lines and their paired tumor segregants, showed some critical regions were non-randomly eliminated, including the 9q22 .1 and 9q22 .3 regions. Conclusions: These results indicate several chromosome 9q regions may contain important TSGs for EC. These functional complementation experiments are expected to map the putative TSGs of EC.