Basic Strategy for the treatment of kidney cancer : identification and clinical utilization of new tumor suppressor genes or oncogenes closely correlated with VHL gene VHL

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The first purpose is to search the growth factor protein using microarray from kidney cancer cells. With this viewpoint we collaborated with Human Genome Center in the Medical Science Institute, University of Tokyo. We identified HIG2, an oncofetal protein, that is expressed only human kidney cancer cells but not in other organ, which is secreted into blood stream. In addition we identified 3 more candidacy proteins. HIG2 works as a growth factor. It is a secretary protein. Since its antibody suppresses the growth of kidney cancer cells, it can control the multiplication of the human kidney cancer. As it is detected in the blood of the human kidney cancer patient, its usefulness is expected as a tumor marker for the human kidney cancers in the future. Presently this idea is the under examination. The 2nd purpose is to identify the gene that is specifically methylated in human kidney cancers, which has VHL gene mutation. The genes that are methylated works as tumor suppressor genes, lik … More e VHL. These genes are not identified yet. It is elucidated that RASSF1A is methylated in 40% kidney cell cancers. We collaborated with Dr.Minoru Toyota, Sapporo Medical School, for the screening of methylated genes in human kidney cancer. We identified methylated islands, MIRC-1, MIRC-2, MIRC-3 and MIRC-4. With the analyses of MIRC-1, we conformed MIRC-1 as a Homeobox gene, HOXB13. It is revealed this protein is expressed only in the proximal tubules in the kidney. When it is highly expressed, it induces apoptosis in the human kidney cell cancer. Methylation frequency in Hoxb13 is 30% in human kidney cancers. It is expected the application of this gene for gene therapy in the future. In addition it is also applicable as a tumor marker in the blood and the urine with use of methylation in this gene. We try to identify the responsible genes for 3 more methylated islands. The 3rd purpose is DNA comparative genomic hybridization or CGH microarray study for human kidney cancers in collaboration with Dr.Joji Inazawa at the Tokyo Medical and Dental College. The identification of the specifically deleted DNA portion in human kidney cancers was not successful difficult in 30 cell lines. Less