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

在不同转移潜能的黑色素瘤亚系之间进行差异筛选，分离出在它们之间差异表达的几个基因。这些基因中的大多数已经被报道，但有些还没有。在那些。TI241与LRF1和ATF3的转录因子同源，转染低转移亚克隆后，其转移潜能增强，在转移灶中的表达增强。在使用手术切除标本的研究中，其表达在血管浸润的病例中表达更多，并且预期其作为预后预测因子的重要性。同样从使用反义寡核苷酸的研究中，显示T1241与细胞粘附、侵袭、细胞形态和运动有关。特别是细胞粘附被认为与细胞凋亡和体内生长有关。从使用裸鼠的实验中。抑制皮下生长，延长存活期，为将其应用于基因治疗开辟了可能。另一个基因T1227与已报道的基因无同源性，但在不同转移潜能的结肠癌细胞亚系中有差异表达。该基因在结肠癌细胞的高转移性亚系中表达更多。对该基因进行了序列分析，并克隆了T1227的人源同源物T1227 H，通过同源性分析确定了T1227最可能的ORF。我们进一步分离了含有T1227的基因组DNA并分析了其5'上游序列。T124I和T1227有望用于转移潜能和预后的诊断。

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.