INHIBITION OF C-MYC IN BREAST AND OVARIAN-CARCINOMA CELLS BY 1,25-DIHYDROXYVITAMIN-D(3), RETINOIC ACID AND DEXAMETHASONE
INHIBITION OF C-MYC IN BREAST AND OVARIAN-CARCINOMA CELLS BY 1,25-DIHYDROXYVITAMIN-D(3), RETINOIC ACID AND DEXAMETHASONE
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DOI：
10.1097/00001813-199304000-00012
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发表时间：
1993-04-01
影响因子：
2.3
通讯作者：
DEPPE, G
中科院分区：
文献类型：
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作者：
SAUNDERS, DE;CHRISTENSEN, C;DEPPE, G
C-myc原癌基因在乳腺和卵巢肿瘤中的作用和调控正受到越来越多的关注。1，25-二羟基维生素D3(骨化三醇)、维甲酸(RA)和地塞米松(Dex)对c-myc原癌基因的下调与白血病细胞的生长抑制密切相关。骨化三醇、维甲酸和地塞米松在乳腺和妇科肿瘤细胞中具有抗增殖活性；然而，这些药物在乳腺癌和卵巢癌中对c-myc的调节大多尚不清楚。我们采用了一种新的方法，利用免疫组织化学方法检测c-myc蛋白，然后用计算机图像分析对c-myc染色进行定量，从而解决了c-myc在这些癌症中的调控问题。该系统代表了蛋白质产品蛋白质印迹分析的一种替代方法，它简单、快速(1天)，可以小规模地进行，并提供了易于对分析数据进行统计分析的样本量。在MCF-7人乳腺癌细胞中，0.5 nM地塞米松、0.01 nM维甲酸和100 nM骨化三醇作用24 h后，c-myc的抑制率分别为29%、45%和54%。在相同激素浓度下，地塞米松、维甲酸和骨化三醇处理3天后，生长抑制率分别为18%、18%和39%(P<；0.05)。T47D人乳腺癌细胞和NIH：OVCAR3人卵巢癌细胞的生长和c-myc抑制模式相似，但T47D细胞的地塞米松对c-myc和c-myc的生长无抑制作用。在MCF-7、NIH：OVCAR3和T47D细胞中的平行对照实验表明，这三种激素都没有抑制上皮膜抗原，这是一种非生长相关蛋白。这表明荷尔蒙对c-myc的表达有特定的影响。综上所述，本研究表明骨化三醇、维甲酸和地塞米松在乳腺和卵巢癌细胞系中抑制c-myc的表达，而这些激素剂也抑制生长，并提示这些激素剂对所研究的乳腺癌和卵巢癌系中c-myc的表达和生长有相应的影响。
The role and regulation of the c-myc protooncogene in breast and ovarian neoplasms is receiving increased attention. The downregulation of the c-myc protooncogene by 1,25-dihydroxyvitamin D3 (calcitriol), retinoic acid (RA) and dexamethasone (Dex) is closely associated with growth inhibition in leukemic cells. Calcitriol, RA and Dex have anti-proliferative activity in breast and gynecologic carcinoma cells; however, the regulation of c-myc by these agents in breast and ovarian cancers is mostly unknown. We have addressed the regulation of c-myc in these cancers using an adaptation of a novel method which employs an immunohistochemical procedure to detect c-myc protein followed by quantification of c-myc staining with computerized image analysis. This system represents an alternative to protein product assay by Western blotting and is straightforward, rapid (1 day), can be carried out on a small scale and provides a sample size that readily facilitates statistical analysis of assay data. In MCF-7 human breast cancer cells, c-myc was suppressed 29% by 0.5 nM Dex, 45% by 0.01 nM RA and 54% by 100 nM calcitriol after 24 h of drug treatment. At the same hormone concentrations, growth was inhibited 18% by Dex, 18% by RA and 39% by calcitriol after 3 days of treatment (p < 0.05 for all hormones). Similar patterns of growth and c-myc inhibition were seen in T47D human breast cancer cells and NIH:OVCAR3 human ovarian cancer cells, with the exception of Dex in T47D cells, which caused no inhibition of c-myc or growth. Parallel control experiments in MCF-7, NIH:OVCAR3 and T47D cells showed that none of the three hormones suppressed epithelial membrane antigen, a non-growth-related protein. This suggested that the hormones specifically influenced c-myc expression. In conclusion, this study has shown that c-myc was repressed by calcitriol, RA and Dex in breast and ovarian carcinoma lines where these same hormonal agents also inhibit growth, and suggests that these hormonal agents have commensurate effects on c-myc expression and growth in the breast and ovarian carcinoma lines examined.