The role of transforming growth factor-β in the regulation of estrogen receptor expression in the MCF-7 breast cancer cell line

Adriana Stoica, Miguel Saceda, Amina Fakhro, Harrison B. Solomon, Bradley D. Fenster, Mary Beth Martin

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    Abstract

    The role of transforming growth factor-β1 (TGFβ1) in the regulation of estrogen receptor (ER) expression in MCF-7 cells was investigated. After treatment of the cells with 100 pM TGFβ1, ER protein declined by about 30% at 6 h from a concentration of 413.5 fmol/mg protein in control cells to 289.5 fmol/mg protein in treated cells. The concentration of receptor remained suppressed for 24 h. Scatchard analysis demonstrated that the decrease in ER protein corresponded to a decrease in estradiol-binding sites, with no effect on the binding affinity of the ER. The dissociation constant of the estradiol-ER complex was 0.117 nM in TGFβ1-treated cells compared to 0.155 nM in control cells. Treatment with TGFβ1 did not influence the half- life of the ER. In TGFβ1-treated cells, as well as in control cells, the half-life of the receptor was approximately 4 h. In contrast to the effect on ER concentration, TGFβ1 treatment resulted in a greater decrease in the steady state level of ER messenger RNA (~75%) at 6 h. By 24 h, a small recovery in the amount of messenger RNA was observed. Transcription run-on experiments demonstrated a decrease of approximately 70% in the level of ER gene transcription at 3 h. Transient transfections using an ER promoter- chloramphenicol acetyltransferase construct demonstrated that after TGFβ1 treatment, chloramphenicol acetyltransferase activity decreased by 50%, suggesting that TGFβ1 inhibition of the ER gene transcription is mediated through the ER promoter. Although treatment with TGFβ1 decreased the ER concentration, the growth factor had no effect on the activity of ER, as measured by its effects on estradiol induction of progesterone receptor and pS2, suggesting that TGFβ1 does not inhibit proliferation of MCF-7 cells by blocking ER activity.

    Original languageEnglish
    Pages (from-to)1498-1505
    Number of pages8
    JournalEndocrinology
    Volume138
    Issue number4
    DOIs
    Publication statusPublished - 1 Jan 1997

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    ASJC Scopus subject areas

    • Endocrinology

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