A ligand of peroxisome proliferator-activated receptor γ, retinoids, and prevention of preneoplastic mammary lesions
A ligand of peroxisome proliferator-activated receptor γ, retinoids, and prevention of preneoplastic mammary lesions
复制标题
DOI：
10.1093/jnci/92.5.418
复制
发表时间：
2000-03-01
期刊：
影响因子：
--
通讯作者：
Koeffler, HP
中科院分区：
文献类型：
--
作者：
Mehta, RG;Williamson, E;Koeffler, HP
背景：乳腺癌的化学预防是一个活跃的研究领域。最近的体内和体外研究表明，噻唑烷二酮（例如，曲格列酮）和类维生素A能够抑制乳腺癌细胞的生长，曲格列酮通过过氧化物酶体增殖物激活受体γ（PPAR γ）介导其作用。我们在小鼠乳腺器官培养模型中评价了曲格列酮单独或与类维生素A联合使用预防7，12-二甲基苯并[a]蒽（DMBA）诱导癌前病变的能力。方法：BALB/c小鼠乳腺用DMBA（2 μ g/ mL）处理，在器官培养中诱导癌前病变。评价了曲格列酮、全反式维甲酸（维甲酸;维甲酸受体[RAR] α配体）和LG 10068（类维生素A X受体[RXR]配体）单独或联合给药对病变发展的影响。类视色素受体（RAR α）的表达。和RXR α）和过氧化物酶体增殖物激活物受体γ通过蛋白质印迹分析测定。通过使用GENCAT软件程序和Bonferroni校正的广义卡方分析确定统计学显著性。结果：曲格列酮（10（-5）M）或维甲酸（10（-6）M）显著抑制乳腺病变的发展（均为P值
Background: Chemoprevention of breast cancer is an active area of investigation. Recent in vivo and in vitro studies have shown that thiazolidinediones (e.g., troglitazone) and retinoids are able to inhibit the growth of breast cancer cells, Troglitazone mediates its action via peroxisome proliferator activated receptor gamma (PPAR gamma). We evaluated the ability of troglitazone, alone or in combination with retinoids, to prevent the induction of preneoplastic lesions by 7,12-dimethylbenz[a]anthracene (DMBA) in a mouse mammary gland organ culture model. Methods: Mammary glands of BALB/c mice were treated with DMBA (2 mu g/ mL) to induce preneoplastic lesions in organ culture. Effects of troglitazone, all-trans-retinoic acid (retinoic acid; ligand for retinoic acid receptor [RAR] alpha) and LG10068 (ligand for retinoid X receptors [RXRs]), singly or in combination, on the development of lesions were evaluated. Expression of retinoid receptors (RAR alpha. and RXR alpha) and PPAR gamma was determined by western blot analysis. Statistical significance was determined by generalized chisquared analysis using the GENCAT software program and Bonferroni correction. All P values are two-sided, Results: Troglitazone (at 10(-5) M) or retinoic acid (at 10(-6) M) markedly inhibited the development of mammary lesions (both P values