Apoptosis and APC in colorectal tumorigenesis
Apoptosis and APC in colorectal tumorigenesis
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DOI：
10.1073/pnas.93.15.7950
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发表时间：
1996-07-23
影响因子：
11.1
通讯作者：
Kinzler, KW
中科院分区：
文献类型：
--
作者：
Morin, PJ;Vogelstein, B;Kinzler, KW
肿瘤是由于调节细胞出生和死亡的体内平衡机制被破坏而引起的。在结肠癌中，这种不平衡的最早表现之一是息肉的形成，这是由人类和小鼠中腺瘤性结肠息肉病（APC）肿瘤抑制基因的体细胞和遗传突变引起的。虽然APC在肿瘤发生中的重要性已被充分证明，但它如何预防肿瘤仍然是一个谜。使用一种新的诱导型表达系统，我们表明，APC在人大肠癌细胞中的表达含有内源性失活APC等位基因的结果在细胞生长的大幅减少。进一步的评估表明，这是由于通过细胞凋亡诱导细胞死亡。这些结果表明，细胞凋亡不仅在晚期肿瘤中起作用，而且在肿瘤形成的最早阶段也起作用。
Tumors result from disruptions in the homeostatic mechanisms that regulate cell birth and cell death. In colon cancer, one of the earliest manifestation of this imbalance is the formation of polyps, caused by somatic and inherited mutations of the adenomatous polyposis coli (APC) tumor suppressor gene in both humans and mice. While the importance of APC in tumorigenesis is well documented, how it functions to prevent tumors remains a mystery. Using a novel inducible expression system, we show that expression of APC in human colorectal cancer cells containing endogenous inactive APC alleles results in a substantial diminution of cell growth. Further evaluation demonstrated that this was due to the induction of cell death through apoptosis. These results suggest that apoptosis plays a role not only in advanced tumors but also at the very earliest stages of neoplasia.