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p53、c-Ha-ras蛋白和佛波酯对兔半乳糖凝集素-3基因表达的调控

Modulation of the expression of the rabbit galectin-3 gene by p53 and c-Ha-ras proteins and PMA.

作者信息

Gaudin J C, Arar C, Monsigny M, Legrand A

机构信息

Centre de Biophysique Moléculaire, CNRS and Université d'Orléans, France.

出版信息

Glycobiology. 1997 Dec;7(8):1089-98. doi: 10.1093/glycob/7.8.1089.

Abstract

Galectin-3 is a galactose-binding lectin that has been found in several mammalian tissues. Galectin-3 gene is expressed in a wide range of normal and tumoral cells. In the case of myeloid cells, its expression correlates with the differentiation of monocytes to macrophages. In the case of cancer cell lines, its expression correlates with tumorigenicity and metastatic potential. The regulation of the expression of this gene is still largely unknown. The rabbit galectin-3 gene has been isolated and characterized. Its structure revealed an organization similar to that of the murine galectin-3 gene. The genomic sequences located upstream from its 5' end, upon insertion upstream from a promoter-free reporter gene, exhibited a strong promoter activity. This activity was upregulated upon treatment of transfected smooth muscle cells with phorbol 12-myristate 13-acetate (PMA) as well as upon transfection with a EJ/ras encoding plasmid. Conversely, it was downmodulated upon transfection with wild-type p53 but not with mutated p53. The regulatory sequences involved in the positive regulation of the gene were located upon serial deletion experiments.

摘要

半乳糖凝集素-3是一种已在多种哺乳动物组织中发现的半乳糖结合凝集素。半乳糖凝集素-3基因在广泛的正常细胞和肿瘤细胞中表达。在髓样细胞中,其表达与单核细胞向巨噬细胞的分化相关。在癌细胞系中,其表达与致瘤性和转移潜能相关。该基因表达的调控在很大程度上仍不清楚。兔半乳糖凝集素-3基因已被分离和鉴定。其结构显示出与小鼠半乳糖凝集素-3基因相似的组织形式。位于其5'端上游的基因组序列,在插入无启动子报告基因上游后,表现出强大的启动子活性。在用佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)处理转染的平滑肌细胞以及用编码EJ/ras的质粒转染后,这种活性被上调。相反,在用野生型p53转染时它被下调,但用突变型p53转染时则不然。通过系列缺失实验确定了参与该基因正调控的调控序列。

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