Sasahara R M, Takahashi C, Sogayar M C, Noda M
Instituto de Química, Universidade de São Paulo, Brasil.
Braz J Med Biol Res. 1999 Jul;32(7):891-5. doi: 10.1590/s0100-879x1999000700014.
The RECK gene was initially isolated as a transformation suppressor gene encoding a novel membrane-anchored glycoprotein and later found to suppress tumor invasion and metastasis by regulating matrix metalloproteinase-9. Its expression is ubiquitous in normal tissues, but undetectable in many tumor cell lines and in fibroblastic lines transformed by various oncogenes. The RECK gene promoter has been cloned and characterized. One of the elements responsible for the oncogene-mediated downregulation of mouse RECK gene is the Sp1 site, where the Sp1 and Sp3 factors bind. Sp1 transcription factor family is involved in the basal level of promoter activity of many genes, as well as in dynamic regulation of gene expression; in a majority of cases as a positive regulator, or, as exemplified by the oncogene-mediated suppression of RECK gene expression, as a negative transcription regulator. The molecular mechanisms of the down-regulation of mouse RECK gene and other tumor suppressor genes are just beginning to be uncovered. Understanding the regulation of these genes may help to develop strategies to restore their expression in tumor cells and, hence, suppress the cells' malignant behavior.
RECK基因最初作为一种编码新型膜锚定糖蛋白的转化抑制基因被分离出来，后来发现它通过调节基质金属蛋白酶-9来抑制肿瘤侵袭和转移。它在正常组织中普遍表达，但在许多肿瘤细胞系和由各种癌基因转化的成纤维细胞系中无法检测到。RECK基因启动子已被克隆和鉴定。负责癌基因介导的小鼠RECK基因下调的元件之一是Sp1位点，Sp1和Sp3因子结合于此。Sp1转录因子家族参与许多基因启动子活性的基础水平以及基因表达的动态调节；在大多数情况下作为正调节因子，或者，如癌基因介导的RECK基因表达抑制所示，作为负转录调节因子。小鼠RECK基因和其他肿瘤抑制基因下调的分子机制才刚刚开始被揭示。了解这些基因的调节可能有助于制定策略来恢复它们在肿瘤细胞中的表达，从而抑制细胞的恶性行为。
