RhoGDI2: a new metastasis suppressor gene: discovery and clinical translation.
The greatest risk for morbidity and mortality caused by bladder cancer is due to metastasis. For this reason, we have developed a paradigm for discovering the molecular mechanisms underlying bladder cancer progression to an invasive and metastatic phenotype. Results of microarray gene expression analysis of a cell culture model were parsed by identifying overlapping genes that correlate with increasing stage and grade of human tumors. One gene identified by this method, RhoGDI2, was tested in various in vitro and in vivo model systems and confirmed to be a metastasis suppressor gene. Using a similar strategy of gene identification by concordance of microarray gene expression results from cells expressing RhoGDI2 and human bladder cancers, two molecular effectors of RhoGDI2 signaling were identified. These targets, endothelin-1 and Neuromedin U are excellent potential targets for therapeutic intervention in the metastatic cascade.
Harding
Michael A
MA
Department of Urology, University of Virginia, Charlottesville, VA 22908, USA.
Theodorescu
Dan
D
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D051381:Rats; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors