Overexpression of bamacan/SMC3 causes transformation
Overexpression of bamacan/SMC3 causes transformation
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DOI：
10.1074/jbc.c000213200
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发表时间：
2000-07-07
影响因子：
4.8
通讯作者：
Iozzo, RV
中科院分区：
文献类型：
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作者：
Ghiselli, G;Iozzo, RV
Bamacan 可以作为组装到基底膜中的分泌蛋白多糖或作为称为 3 号染色体结构维持 (SMC3) 的细胞内蛋白出现在某些细胞类型中。为了评估该蛋白在肿瘤发生中的作用，我们研究了诱导的 bamacan/SMC3 过度表达是否可以转化正常成纤维细胞。我们生成了编码整个小鼠 bamacan/SMC3 的全长 cDNA，并证明了其能够适当转录和翻译成 146 kDa 蛋白质。所有过度表达 bamacan/SMC3 转基因的 NIH 和 Balb/c 3T3 鼠成纤维细胞均产生转化灶并获得了贴壁依赖性生长。转染的成纤维细胞中bamacan/SMC3表达水平的增加与在一系列自发转化的鼠和人结肠癌细胞中检测到的水平相同。此外，在配对的人类结肠癌标本中（n = 19，p < 0.0002）和 Apc 缺陷 Min/+ 小鼠的肠道肿瘤队列中，大约 70% 的 bamacan/SMC3 过表达被检测到 3-4 倍。这些结果支持这样的概念：bamacan/SMC3 的表达失调参与细胞转化。
Bamacan can occur in certain cell types as either a secreted proteoglycan assembled into basement membranes or as an intracellular protein known as structural maintenance of chromosome 3 (SMC3). To assess the role of this protein in tumorigenesis, we investigated whether induced overexpression of bamacan/SMC3 could transform normal fibroblasts. We generated a full-length cDNA encoding the entire mouse bamacan/SMC3 and demonstrated appropriate transcription and translation into a 146-kDa protein. AU the NIH and Balb/c 3T3 murine fibroblasts overexpressing this bamacan/SMC3 transgene generated foci of transformation and acquired anchorage-independent growth. The increased levels of bamacan/SMC3 expression achieved in the transfected fibroblasts were the same as those detected in a series of spontaneously transformed murine and human colon carcinoma cells. Moreover, a 3-4-fold overexpression of bamacan/SMC3 was detected in similar to 70% of human colon carcinoma specimens from matched pairs (n = 19, p < 0.0002) and in a cohort of intestinal tumors from Apc-deficient Min/+ mice. These results support the concept that deregulated expression of bamacan/SMC3 is involved in cell transformation.