Kavanaugh Claudine, Green Jeffrey E
Laboratory of Cellular Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA.
J Nutr. 2003 Jul;133(7 Suppl):2404S-2409S. doi: 10.1093/jn/133.7.2404S.
Chemoprevention through nutritional and dietary changes may offer an important means of inhibiting the development and progression of breast cancer, which would have a major impact on public health. Studies to assess the efficacy of potential chemopreventive compounds are difficult to perform in large human populations, whereas the use of genetically engineered mice (GEM) for preclinical testing offers several advantages. GEM models can be utilized to assess the inhibitory effects of nutritional and chemopreventive agents on well-defined oncogenic signaling pathways. Because several transgenic mouse models progress through a well-defined temporal series of stages leading to invasive carcinoma formation, they may be particularly useful for determining cancer stage-specific responses to nutritional and chemopreventive agents. The C3(1)SV40 T/t-antigen transgenic mouse mammary cancer model has been utilized for chemopreventive research in which mammary tumors develop over a well-characterized time course. Several compounds have been shown to inhibit mammary tumor development in this model, including retinoids, di-fluoromethylornithine (DFMO), dehydroepiandrosterone (DHEA), antiangiogenic compounds and nonsteroidal antiinflammatory drugs (NSAID). All of the chemopreventive agents used in the C3(1)Tag mammary mouse model appear to affect the promotion stage of tumorigenesis, suggesting that these agents may be useful in inhibiting the transition of human ductal carcinoma in situ (DCIS) to invasive carcinoma. Selective combinations of chemopreventive agents may be particularly useful for targeting multiple signaling pathways involved in cancer development and progression leading to improved clinical responses. The application of gene expression profiling to chemopreventive studies will aid in the selection of appropriate models for preclinical testing and further define mechanisms of action.
通过营养和饮食改变进行化学预防可能是抑制乳腺癌发生和发展的重要手段，这将对公众健康产生重大影响。在大量人群中评估潜在化学预防化合物疗效的研究很难开展，而利用基因工程小鼠（GEM）进行临床前测试具有诸多优势。GEM模型可用于评估营养和化学预防剂对明确的致癌信号通路的抑制作用。由于几种转基因小鼠模型会经历一系列明确的阶段，最终形成浸润性癌，因此它们在确定癌症特定阶段对营养和化学预防剂的反应方面可能特别有用。C3(1)SV40 T/t-抗原转基因小鼠乳腺癌模型已用于化学预防研究，在该模型中乳腺肿瘤会在一个特征明确的时间进程中发展。已证明几种化合物可抑制该模型中的乳腺肿瘤发展，包括类视黄醇、二氟甲基鸟氨酸（DFMO）、脱氢表雄酮（DHEA）、抗血管生成化合物和非甾体抗炎药（NSAID）。在C3(1)Tag乳腺小鼠模型中使用的所有化学预防剂似乎都影响肿瘤发生的促进阶段，这表明这些药物可能有助于抑制人类原位导管癌（DCIS）向浸润性癌的转变。化学预防剂的选择性组合可能对靶向参与癌症发生和发展的多个信号通路特别有用，从而改善临床反应。将基因表达谱分析应用于化学预防研究将有助于选择合适的临床前测试模型，并进一步明确作用机制。
