ヒト・ホメオドメインタンパクによる新しいカドヘリン遺伝子の発現制御機構の解析

我们从人类基因组文库中分离出2号染色体上的同源异型盒基因Hoxd3，并测定了其核苷酸序列。在本研究中，为了研究Hoxd3基因在红细胞生成中的作用，将Hoxd3基因正、反义定向的表达载体导入HEL细胞。高表达Hoxd3基因的正义转染体形成聚集体，由紧密结合的细胞附着在组织培养皿上，而亲本HEL细胞和反义转染体附着在培养皿上较差。此外，高表达Hoxd3基因的正义转染体比反义转染体和亲本HEL细胞更有效地与纤维连接蛋白和胶原结合。Northern印迹分析表明，在高表达HOX4A基因的HEL细胞中，整合素Beta3的mRNA水平显著增加。流式细胞仪分析表明，正义转染体表达的整合素αIIβ3复合体水平增加。反义转染组较正义转染组和亲本HEL细胞表达更丰富的R-钙粘蛋白。这些结果表明同源异型盒基因Hoxd3参与了细胞黏附过程的调节。

We isolated the human homeobox gene HOXD3 on chromosome 2 from a human genomic library and determined its nucleotide sequence. In the present study, in order to study the role of the HOXD3 gene in erythropoiesis, expression vectors containing the HOXD3 gene inthe sense or antisense orientation were introduced into HEL cells. The sensetransfectants overexpressing the HOXD3 gene formed aggregates, which were composed of densely associated cells adhering to tissue-culture dishes, whereas the parental HEL cells and antisense transfectants adhered poorly to the dishes. Furthermore, the sense transfectants overexpressing the HOXD3 gene attached more efficiently to fibronectin and collagen than did the antisense transfectants and parental HEL cells. Northern blot analysis showed that integrin beta3 mRNA levels were significantly increased in the HEL cells overexpressing the HOX4A gene. FACS analysis showed that the sense transfectants expressed increased levelsof integrin alpha II bbeta3 complex. In addition, the antisense transfectants expressed R-cadherin more abundantly than the sense transfectants and parental HEL cells. These results implicate the homeobox gene HOXD3 in the regulation of cell abhesion processes.