Retinoid receptor-dependent and -independent effects of N-(4-hydroxyphenyl)retinamide in F9 embryonal carcinoma cells.
Retinoid receptor-dependent and -independent effects of N-(4-hydroxyphenyl)retinamide in F9 embryonal carcinoma cells.
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发表时间：
1999
期刊：
影响因子：
11.2
通讯作者：
J. Clifford;D. Menter;Michael Wang;R. Lotan;S. Lippman
中科院分区：
文献类型：
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作者：
J. Clifford;D. Menter;Michael Wang;R. Lotan;S. Lippman
芬维A胺（Fenretinide，4HPR）是一种具有抗肿瘤和化学预防活性的维甲酸类似物。4HPR的作用机制尚不完全清楚，但假设该化合物的作用独立于核维甲酸受体途径。为了直接验证这一假设，我们分析了4HPR对一组F9胚胎癌细胞系的活性，其中包括缺乏视黄酸受体γ、类维生素A X受体α或两者表达的野生型和突变株。4HPR（10 μ M）处理导致F9细胞中的细胞死亡的快速诱导，这是它们在48小时内几乎消除的原因。这种效应也发生在受体缺失的细胞系中。用1 μ M 4HPR处理野生型细胞4天也导致原始内胚层分化表型，其通常在全反式视黄酸处理后观察到，并且特征在于层粘连蛋白B1和IV型胶原的上调。这种分化反应没有发生在受体无效的细胞。因此，在该系统中鉴定了4HPR的两种不同作用：快速诱导细胞死亡和较慢诱导分化，这可能分别是受体非依赖性和依赖性的。
Fenretinide (N-[4-hydroxyphenyl]retinamide (4HPR)) is a retinoid analogue with antitumor and chemopreventive activities. The mechanism of action of 4HPR is not fully understood, but it is hypothesized that this compound acts independently of the nuclear retinoid receptor pathway. To test this hypothesis directly, we have analyzed the activity of 4HPR on a panel of F9 embryonal carcinoma cell lines, which includes wild-type and mutant lines that lack expression of retinoic acid receptor gamma, retinoid X receptor alpha, or both. 4HPR (10 microM) treatment resulted in a rapid induction of cell death in F9 cells, which was responsible for their near elimination by 48 h. This effect occurred in the receptor-null cell lines as well. Treatment of the wild-type cells for 4 days with 1 microM 4HPR also resulted in a primitive endodermal differentiated phenotype that is normally seen upon all-trans-retinoic acid treatment and is characterized by the up-regulation of laminin B1 and type IV collagen. This differentiation response did not occur in the receptor-null cells. Therefore, two distinct effects of 4HPR were identified in this system: a rapid induction of cell death and a slower induction of differentiation, which are likely to be receptor independent and dependent, respectively.