Nuclear overexpression of the oncoprotein β-catenin in colorectal cancer is localized predominantly at the invasion front
Nuclear overexpression of the oncoprotein β-catenin in colorectal cancer is localized predominantly at the invasion front
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DOI：
10.1016/s0344-0338(98)80129-5
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发表时间：
1998-01-01
影响因子：
2.8
通讯作者：
Kirchner, T
中科院分区：
文献类型：
--
作者：
Brabletz, T;Jung, A;Kirchner, T
60% - 80%的所有结直肠癌都以APC肿瘤抑制基因的突变作为特征。最近，有研究表明这些突变通过破坏无翅型/ WNT信号通路导致β - 连环蛋白在细胞核内过度表达。由于细胞核内的β - 连环蛋白作为迄今未知的肿瘤基因的转录激活因子发挥作用，这种形式的β - 连环蛋白现在被认为是结直肠癌中的一种主要癌蛋白。我们利用免疫组织化学方法研究了过度表达的β - 连环蛋白在单个结直肠癌中的分布情况。在大多数肿瘤中，我们没有发现均匀染色，而是β - 连环蛋白在细胞核内强烈表达，且主要定位于肿瘤浸润前沿，孤立、分散的肿瘤细胞的细胞核染色最强。相反，肿瘤中心的细胞往往没有细胞核染色，但保留了β - 连环蛋白的膜表达，这与正常结肠上皮细胞相似。因此，除了由APC基因座缺陷导致的β - 连环蛋白过度表达外，肿瘤自身的调节事件可能导致这种癌蛋白的不同分布。可能是浸润前沿的周围组织能够向肿瘤细胞发出信号，导致β - 连环蛋白发生核转位，在那里它可能在肿瘤浸润过程中发挥直接作用。
Sixty to eighty percent of all colorectal cancers are characterized by mutations in the APC tumor suppressor gene. Recently, it was shown that these mutations lead to a nuclear overexpression of beta-Catenin by disruption of the wingless/WNT signal pathway. Since nuclear beta-Catenin functions as a transcriptional activator of hitherto unknown tumor genes, this form of beta-Catenin is now considered a major oncoprotein in colorectal cancer. Using immunohistochemistry, we investigated the distribution of overexpressed beta-Catenin within individual colorectal carcinomas. In the majority of the tumors, we found no homogeneous staining, but a strong nuclear expression of beta-Catenin predominantly localized at the invasion front with strongest nuclear staining of isolated, scattered tumor cells. In contrast, cells in the tumor center often showed no nuclear staining, but retained a membranous expression of beta-Catenin, comparable to normal colon epithelium. It is, therefore, likely that in addition to the overexpression of beta-Catenin caused by defects in the APC locus, regulatory events in the tumor itself lead to a different distribution of this oncoprotein. Possibly, surrounding tissue at the invasion front can give signals to the tumor cells, leading to a nuclear translocation of beta-Catenin, where it may play a direct role in tumor invasion processes.