Expression of nuclear β-catenin and c-myc is correlated with tumor size but not with proliferative activity of colorectal adenomas
Expression of nuclear β-catenin and c-myc is correlated with tumor size but not with proliferative activity of colorectal adenomas
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DOI：
10.1016/s0002-9440(10)64955-3
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发表时间：
2000-03-01
影响因子：
6
通讯作者：
Kirchner, T
中科院分区：
文献类型：
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作者：
Brabletz, T;Herrmann, K;Kirchner, T
大多数结直肠癌的腺瘤性息肉病 (APC) 抑癌基因存在功能缺失突变。这导致核 β-连环蛋白的积累，它与 DNA 结合蛋白 TCF-4 一起发挥转录激活剂的作用。最近定义的靶基因 c-myc、cyclin D1 和 matrilysin 负责肿瘤增殖或恶性进展，并解释了核 β-catenin 的致癌潜力。为了研究其在早期结肠癌发生中的作用，我们分析了 88 个不同大小和不典型增生级别的结直肠腺瘤中 β-catenin 的表达、其靶基因 c-myc 以及增殖活性。结果显示，i）核β-连环蛋白和c-myc表达最显着的相关性是凝块与不典型增生的程度，但与结肠腺瘤的大小； ii) 核β-连环蛋白和c-myc 表达的完美相关性； iii) 腺瘤大小与增殖活性无显着相关性； iv) 增殖活性与β-连环蛋白和c-myc 的核表达没有显着相关性。这些结果表明 APC 突变具有额外的不依赖于 β-连环蛋白的功能；单独的 APC 突变不足以导致 β-连环蛋白的核过度表达；核β-连环蛋白对于超过肿瘤大小阈值具有额外的重要功能。
Most colorectal cancers have loss-of-function mutations in the adenomatosis polyposis coli (APC) tumor suppressor gene. This leads to the accumulation of nuclear beta-catenin, which, together with the DNA-binding protein TCF-4, functions as a transcriptional activator. The recently defined target genes c-myc, cyclin D1, and matrilysin are responsible for tumor proliferation or malignant progression and explain the oncogenic potential of nuclear beta-catenin. To investigate its role in early colon carcinogenesis, we analyzed the expression of beta-catenin, its target gene c-myc, and the proliferative activity in 88 colorectal adenomas of varying size and grade of dysplasia. The results revealed i) the most significant correlation of nuclear beta-catenin and c-myc expression was clot with the grade of dysplasia but with the size of the colon adenoma; ii) perfect correlation of nuclear beta-catenin and c-myc expression; iii) no significant correlation of adenoma size with the proliferative activity; and iv) no significant correlation of proliferative activity and the nuclear expression of beta-catenin and c-myc. These results imply that APC mutations have additional beta-catenin-independent functions; APC mutations alone are not sufficient for nuclear overexpression of beta-catenin; and nuclear beta-catenin has additional important functions for exceeding a threshold tumor size.