|Function and cDNA Resources Section
DOE Human Genome Program Contractor-Grantee
107. Ribozyme Gene Vector Libraries Identify Putative Tumor Suppressor Genes
Qi-Xiang Li, Eric Marcusson, Joan Robbins, Mark Leavitt, Flossie Wong-Staal, and Jack R. Barber
Immusol, Inc. San Diego, CA 92121 and University of California, San Diego, CA
We have developed a method for gene identification, based on analysis of cellular function, that allows the specific, directed identification and cloning of many genes. We have created viral vectors containing a highly complex library of Rz genes that can be stably and efficiently introduced into mammalian cells. By utilizing methodologies that enable selection of cells that have undergone a phenotypic change as a result of a specific Rz, we can isolate Rzs that inactivate genes associated with that phenotype. Once specific Rzs are selected and verified, their target recognition binding sequences can be used as tags to identify and clone the corresponding target genes.
We have used this approach to identify three novel tumor suppressor genes. We will present evidence that validates the role of these genes in the process of malignant transformation. Furthermore, we have used RNA expression profiling to begin the functional dissection of the pathways that these genes are involved in.
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