β-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer
β-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer
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DOI：
10.1016/s0002-9440(10)65204-2
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发表时间：
1999-10-01
影响因子：
6
通讯作者：
Kirchner, T
中科院分区：
文献类型：
--
作者：
Brabletz, T;Jung, A;Kirchner, T
大多数结直肠癌具有腺瘤病息肉病(APC)抑癌基因的功能突变。这会导致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的作用。最近确定的靶基因是c-myc和细胞周期蛋白D1，它们将APC基因缺陷与结肠肿瘤的自主增殖能力联系起来。在这里，我们报告了基质金属蛋白酶-7作为β-连环蛋白/TCF-4的另一个靶基因的鉴定。MMP7在80%的人类结直肠癌中高表达，被认为是早期肿瘤生长的重要因素，对晚期进展也有潜在作用，如侵袭和转移。我们的结果解释了在结肠肿瘤中高比例的基质金属蛋白酶-7过度表达。此外，他们表明，APC肿瘤抑制基因的缺陷也可能对结肠癌进展的后期步骤产生影响。
Most colorectal cancers have loss of function mutations in the adenomatosis polyposis coli (APC) tumor suppressor gene. This leads to accumulation of beta-catenin, which together with the DNA binding protein TCF-4 functions as a transcriptional activator. Recently defined target genes are c-myc and cyclin D1, linking the APC gene defect to the capacity for autonomous proliferation of colon tumors. Here we report the identification of the matrix metalloproteinase MMP-7 as another target gene of beta-catenin/TCF-4. MMP-7 is overexpressed in 80% of human colorectal cancers and known to be an important factor for early tumor growth, with a potential function also for later progression steps, like invasion and metastasis. Our results explain the high percentage of MMP-7 overexpression in colon tumors. Moreover they indicate that defects in the APC tumor suppressor gene may also have an influence on later steps of colon tumor progression.