BINDING OF RETINOIDS TO HUMAN-BREAST CANCER CELL-LINES AND THEIR EFFECTS ON CELL-GROWTH
BINDING OF RETINOIDS TO HUMAN-BREAST CANCER CELL-LINES AND THEIR EFFECTS ON CELL-GROWTH
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DOI：
10.1172/jci109703
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发表时间：
1980-01-01
影响因子：
15.9
通讯作者：
LIPPMAN, ME
中科院分区：
文献类型：
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作者：
LACROIX, A;LIPPMAN, ME
维生素A及其类似物(维甲酸)调节上皮组织的分化。维甲酸在体内抑制致癌物诱导的大鼠乳腺癌，在一些人乳腺癌样本中已经证实了维甲酸的细胞结合蛋白。在这项研究中，研究了长期组织培养的人乳腺癌细胞系模型系统中维甲酸对生长的影响和细胞维甲酸结合蛋白的存在。视黄酸和视黄醇可抑制MCF-7、Hs578T和ZR-75-B细胞的生长。在这方面，维甲酸比视黄醇更有效：6 nM维甲酸在ZR-75-B中达到50%的生长抑制，在MCF-7和Hs578T中达到700 nM，而所有3种细胞株都需要5-8 nM视黄醇。不同细胞系生长抑制开始的时间明显不同，与细胞密度或倍增时间无关。维甲酸使MCF-7和ZR-75-B的倍增时间增加2~3倍，但可导致Hs578T细胞死亡。通过去除维甲酸，这种生长抑制在每种细胞系中都是可逆的。用蔗糖密度梯度离心法测定MCF-7和Hs578T细胞胞浆中的[~3H]维甲酸和[~3H]维甲醇有明显的结合。在ZR-75-B中，存在[~3H]维甲酸结合，但没有检测到[~3H]视黄醇结合。维甲酸可能在人类乳腺癌的调节和治疗中发挥重要作用，人类乳腺癌细胞系是研究这一作用的有用模型。
Vitamin A and its analogs (retinoids) regulate the differentiation of epithelial tissues. Retinoids inhibit the induction of rat mammary cancers by carcinogens in vivo, and cellular binding proteins for retinoids have been demonstrated in some human breast cancer samples. In this study, the model system of human breast cancer cell lines in long-term tissue culture was examined for effects of retinoids on growth and for the presence of cellular retinoid binding proteins. Retinoic acid and retinol inhibit the growth of MCF-7, Hs578T and ZR-75-B cell lines. Retinoic acid is more potent than retinol in this regard: 50% growth inhibition is achieved by 6 nM retinoic acid in ZR-75-B and by 700 nM in MCF-7 and Hs578T, whereas 5-8 .mu.M retinol is required in all 3 cell lines. The time to onset of growth inhibition varies markedly between cell lines and is not related to cell density or doubling time. Retinoic acid increases the doubling time of MCF-7 and ZR-75-B by 2- to 3-fold, but causes cell death in Hs578T. The growth inhibition is reversible in every cell line by removal of retinoic acid. Specific and distinct binding of [3H]retinoic acid and [3H]retinol is present in cytosols of MCF-7 and Hs578T cells as assessed by sucrose density gradient centrifugation. In ZR-75-B, [3H]retinoic acid binding was present, but no binding of [3H]retinol was detectable. Retinoids may play an important role in the regulation and treatment of human breast cancer and that human breast cancer cell lines represent a useful model to study this role.