Transcriptional regulation of DF3 gene expression in human MCF-7 breast carcinoma cells

Abstract

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.