The mechanism analysis and practical application of apoptosis induct of metastasis related gene.

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Differenlial screening between melanoma sublines of dirrerent metastatic potentials was performed and several genes were isolated that were differentially expressed between them. Most of these genes were already reported, but some were not. In those. TI241 showed homology with transcription factors of LRF1 and ATF3.Its transaction to the low metastatic subclone strengthened its metastatic potential and its expression in the metastatic foci was elevated. In the study using surgically excised specimens, its expression was expressed more in the cases with vascular invasions and its importance as a prognosis predictor was expected. Also from the study with the antisense oligonuclcolides, T1241 was shown to relate cell adhesion, invasion, cell form and movement. Especially cell adhesion was thought to relate apoptosis and in vivo growth. From the experiments using nude mice. It surpressed subcutaneus growth and lengthened their survival period, which opened a possibility of its application to the gene therapy. Another gene T1227 showed no homology with formaly reported genes and differentally expressed in the sublines of colon cancer cells with different metastatic potential. This gene was expressed more in the highly experimentally metastatic subline of colon cancer cells. We analyzed its sequence and isolated its human counterpart T1227H.From the homology research between T1227 and T1227H, the most possible ORF was determined. We further isolated genomic DNA containing T1227 and analyzed its 5' upstream sequence. T124I and T1227 were expected to be used in the diagnosis of metastatic potential and prognosis.