Morin P J, Vogelstein B, Kinzler K W
The Howard Hughes Medical Institute, Baltimore, MD 21231, USA.
Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7950-4. doi: 10.1073/pnas.93.15.7950.
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.
肿瘤是由调节细胞生成和细胞死亡的稳态机制紊乱所导致的。在结肠癌中，这种失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有充分记录，但其预防肿瘤的作用机制仍是个谜。我们使用一种新型的诱导表达系统表明，在含有内源性无活性APC等位基因的人结肠癌细胞中表达APC会导致细胞生长显著减少。进一步评估表明，这是由于通过凋亡诱导细胞死亡所致。这些结果表明，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。
