Functional analysis in the search for a putative tumor suppressor gene based upon the changes in the expression of membrane proteins in human tumor cells

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Previos studies on human cell hybrids of HeLa and normal fibroblasts indicates that the tumorigenicy may be controlled by a putative tumor suppressor gene on chromosome 11. In this study, we found that tumorigenic cell hybrids express the glucose transporter isoforms GLUT1 and GLUT3 while non-tumorigenic cells express GLUT1 alone. The co-expression of these isoforms was also evident in gamma-ray-induced tumorigenic clones isolated from a non-tumorigenic cell. GLUT3 mRNA was specifically expressed in tumorigenic cell hybrids. When GLUT3 was stably overexpressed, the affinity for 2-deoxyglucose markedly increased. These results suggest that the enhanced GLUT3 expression in HeLa cell hybrids accompanied with the increased affinity for glucose is regulated at the transcriptional level by the dysfunction of the tumor suppressor gene. A possible role of the putative tumor suppressor gene in control of gene expression has been studied using an expression vector containing caveolin promoter linked to the luciferase gene, whose activities were parallel to the caveolin expression in these hybrid cells. Functional regions of the caveolin promoter to control the gene expression are further examined. A new cationic liposome for efficient gene delivery with serum into human tumor cells in vitro and in vivo was also developed during this project.