Merlino G
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892.
Semin Cancer Biol. 1994 Feb;5(1):13-20.
Whether a cell decides to proliferate, undergo growth arrest, or even commit suicide is determined by a multitude of highly potent positive and negative regulatory factors. Mutational perturbation of these factors and the normal pathways through which they regulate either cell proliferation or cell death can induce a pathologic enhancement in cell number, or hyperplasia, and eventually the development of malignant tumors. Serving as valuable animal models for cancer in humans, transgenic mice have been used to demonstrate the dramatic consequences of subverting the normal molecular mechanisms regulating cell proliferation and/or cell death. This review will use three transgenic mouse models to illustrate the consequences of inducing such regulatory imbalances, as well as the utility and versatility of the transgenic approach in cancer research. Three different regulatory factors are considered; transforming growth factor-alpha is discussed as an example of a positive growth regulator, p53 as a negative growth regulator, and Bcl-2 as an inhibitor of programmed cell death.
细胞是决定增殖、进入生长停滞状态甚至自杀，这取决于众多高效的正负调节因子。这些因子以及它们调节细胞增殖或细胞死亡的正常途径发生突变性扰动，可导致细胞数量病理性增加，即增生，最终发展为恶性肿瘤。转基因小鼠作为人类癌症的重要动物模型，已被用于证明颠覆调节细胞增殖和/或细胞死亡的正常分子机制所产生的巨大后果。本综述将使用三种转基因小鼠模型来说明诱导此类调节失衡的后果，以及转基因方法在癌症研究中的实用性和多功能性。我们考虑了三种不同的调节因子；转化生长因子-α作为正性生长调节因子的一个例子进行讨论，p53作为负性生长调节因子，Bcl-2作为程序性细胞死亡的抑制剂。
