Abe M, Kufe D
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
J Cell Physiol. 1990 May;143(2):226-31. doi: 10.1002/jcp.1041430205.
The DF3 gene codes for a high molecular weight human breast tumor-associated glycoprotein. The detection of this antigen in human milk has also suggested that its expression represents a differentiated function of mammary epithelium. The present studies have examined the regulation of DF3 gene expression in human MCF-7 breast carcinoma cells. These cells express two DF3 transcripts of 4.5 and 7.0 kb. Treatment of MCF-7 cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) was associated with increases in levels of both DF3 mRNAs. When nuclear run-on assays were used, DF3 gene transcription was at low to undetectable levels in untreated MCF-7 cells and was increased after TPA exposure. TPA-induced increases in DF3 mRNA levels were also inhibited by actinomycin D (ACT). MCF-7 cells exposed to ACT further demonstrated that the half-lives of the 4.5 and 7.0 kb transcripts are 26 and 11 h, respectively. The results also demonstrate that the protein synthesis inhibitor, cycloheximide (CHX), increases DF3 mRNA levels in MCF-7 cells. These effects of CHX were sensitive to actinomycin D and not associated with stabilization of the DF3 transcripts. Taken together, these findings indicate that DF3 gene expression is controlled at a transcriptional level in TPA- and CHX-treated MCF-7 cells.
DF3基因编码一种高分子量的人乳腺肿瘤相关糖蛋白。在人乳中检测到这种抗原也表明其表达代表了乳腺上皮细胞的一种分化功能。本研究检测了人MCF-7乳腺癌细胞中DF3基因表达的调控情况。这些细胞表达4.5 kb和7.0 kb的两种DF3转录本。用12-0-十四烷酰佛波醇-13-乙酸酯（TPA）处理MCF-7细胞会导致两种DF3 mRNA水平升高。当使用核转录分析时，未处理的MCF-7细胞中DF3基因转录处于低水平至无法检测的水平，TPA处理后转录增加。TPA诱导的DF3 mRNA水平升高也受到放线菌素D（ACT）的抑制。暴露于ACT的MCF-7细胞进一步表明，4.5 kb和7.0 kb转录本的半衰期分别为26小时和11小时。结果还表明，蛋白质合成抑制剂环己酰亚胺（CHX）可增加MCF-7细胞中DF3 mRNA的水平。CHX的这些作用对放线菌素D敏感，且与DF3转录本的稳定性无关。综上所述，这些发现表明在TPA和CHX处理的MCF-7细胞中，DF3基因表达在转录水平受到调控。
