Abstract
Oestrogens and antioestrogens modulate the synthesis of transforming growth factor alpha (TGF-alpha) in breast cancer cells. The purpose of the present report was to examine regulation of TGF-alpha gene expression by oestradiol (E2) and antioestrogens in MDA-MB-231 breast cancer cells transfected with either the wild-type or mutant oestrogen receptor (ER). We recently reported the concentration-dependent E2 stimulation of TGF-alpha mRNA in MDA-MB-231 ER transfectants (Levenson et al, 1997). We now report that 4-hydroxytamoxifen (4-OHT) shows oestrogen-like effects on the induction of TGF-alpha gene expression in our transfectants. Accumulation of TGF-alpha mRNA in response to both E2 and 4-OHT but not in response to the pure antioestrogen ICI 182,780 suggests that E2-ER and 4-OHT-ER complexes can bind to an oestrogen response element (ERE), located in the promoter region of the TGF-alpha gene and can activate transcription of the gene. Surprisingly, no activation of luciferase expression was observed after transient transfection of the TGF-alpha ERE/luciferase reporter constructs. Possible activation of an alternative ER-mediated pathway responsible for the regulation of TGF-alpha gene expression in the ER transfectants is discussed.
Highlights
During our investigation of the growth control mechanisms in the S30 cell line, we discovered that oestrogen causes an increase in the mRNA of transforming growth factor alpha (TGF-a) (Jeng et al, 1994)
We examine the action of 4-OHT on the expression of the TGF-ax gene in these transfectants
Similar to the effect of 4-OHT seen in S30 cells, there was a concentration-dependent induction of TGF-a mRNA in BC-2 cells, expressing mutant oestrogen receptor (ER) (Figure 2B)
Summary
The purpose of the present report was to examine regulation of TGF-a gene expression by oestradiol (E2) and antioestrogens in MDA-MB-231 breast cancer cells transfected with either the wild-type or mutant oestrogen receptor (ER). The aim of this paper is to report progress in new investigations of TGF-a gene regulation by 17p-oestradiol (E2) and antioestrogens in S30 cells (Jiang and Jordan, 1992) and in
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