Muller W J
Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada.
Cancer Metastasis Rev. 1991 Oct;10(3):217-27. doi: 10.1007/BF00050793.
Breast cancer is the leading cause of death among non-smoking women and thus has been the focus of intensive research. It has been generally accepted that the deregulation of oncogenes or their regulators play a pivotal role in progression of this prevalent disease. For example, amplification and overexpression of a number of oncogenes has been observed in a proportion of primary breast cancer biopsies. More recently, there has also been reports of inactivation tumor suppressor genes in human breast cancer. While there is compelling evidence for a role of these genes in breast cancer tumor progression due to limitations inherent in these studies it is difficult to establish a direct causal association between expression of a certain oncogene and tumor progression. For this reason many groups have employed the transgenic mouse as a model system to directly study effects of oncogene expression in the murine mammary gland. This review will attempt to highlight some of the important lessons and potential applications that have emerged from the study of oncogene expression in the mammary epithelium of transgenic mice. The utility of the transgenic system to assess the transforming potential of oncogenes, to investigate the multi-step nature of malignant progression, and to be used as models for therapeutic intervention will be discussed.
乳腺癌是不吸烟女性死亡的主要原因，因此一直是深入研究的焦点。人们普遍认为，癌基因或其调节因子的失调在这种常见疾病的进展中起着关键作用。例如，在一部分原发性乳腺癌活检中观察到了多种癌基因的扩增和过表达。最近，也有关于人类乳腺癌中肿瘤抑制基因失活的报道。虽然有令人信服的证据表明这些基因在乳腺癌肿瘤进展中起作用，但由于这些研究固有的局限性，很难确定某一癌基因的表达与肿瘤进展之间的直接因果关系。因此，许多研究小组将转基因小鼠作为模型系统，直接研究癌基因在小鼠乳腺中的表达效果。本综述将试图突出一些重要的经验教训以及从转基因小鼠乳腺上皮中癌基因表达研究中出现的潜在应用。将讨论转基因系统在评估癌基因转化潜力、研究恶性进展的多步骤性质以及用作治疗干预模型方面的效用。
