Telang N T, Bradlow H L, Osborne M P
Division of Carcinogenesis and Prevention, Strang-Cornell Cancer Research Laboratory, New York, New York 10021.
J Cell Biochem Suppl. 1992;16G:161-9. doi: 10.1002/jcb.240501128.
The animal models for chemoprevention of breast cancer have provided important experimental systems to evaluate the efficacy of tumor suppression by dietary macro- and micronutrients. In the initiation/promotion cascade, early occurring premalignant changes constitute less extensively examined aspects of disease progression. Molecular, endocrine and cellular biomarkers may provide clinically relevant endpoints for prevention of breast cancer that focus on downregulation of preneoplastic transformation. In vitro models derived from non-involved murine and human mammary tissues are utilized to identify molecular, endocrine and cellular markers that are perturbed in response to such diverse initiators as viruses and chemical carcinogens. This upregulation was manifested as persistent Ras p21-GTP binding, altered C16 alpha/C2 hydroxylation of estradiol, and hyperplasia preceding tumorigenesis. Prototypic chemopreventive agents such as n-3 polyunsaturated fatty acids, retinoids, and indole-3-carbinol were capable of downregulating all of the preneoplastic markers perturbed by initiators. Experimental modulation of these biomarkers in murine and human mammary tissue prior to the expression of a fully transformed tumorigenic phenotype is suggestive of their potential clinical application in chemopreventive intervention for breast cancer.
乳腺癌化学预防的动物模型为评估膳食中常量和微量营养素的抑癌功效提供了重要的实验系统。在启动/促进级联反应中，早期发生的癌前变化是疾病进展中较少被广泛研究的方面。分子、内分泌和细胞生物标志物可为乳腺癌预防提供临床相关的终点指标，重点在于下调肿瘤前体细胞转化。源自未受累的小鼠和人类乳腺组织的体外模型用于识别因病毒和化学致癌物等多种启动剂而受到干扰的分子、内分泌和细胞标志物。这种上调表现为持续的Ras p21-GTP结合、雌二醇C16α/C2羟基化改变以及肿瘤发生前的增生。n-3多不饱和脂肪酸、类维生素A和吲哚-3-甲醇等典型化学预防剂能够下调所有因启动剂而受到干扰的肿瘤前体细胞标志物。在完全转化的致瘤表型表达之前，对小鼠和人类乳腺组织中的这些生物标志物进行实验性调节，提示了它们在乳腺癌化学预防干预中的潜在临床应用。
