5-Bromodeoxyuridine specifically inhibits the synthesis of estrogen-induced proteins in MCF7 cells.
In the MCF7 human breast cancer cell line, estrogens induce a secreted glycoprotein with an Mr of 46 000 (46 000-Mr protein) and the progesterone receptor; they also increase to a lesser extent the secretion of [35S]-methionine-labelled proteins. When the cells are grown in the presence of 5-bromo-2'-deoxyuridine (BrdUrd, 5 microgram/ml for 4 days) these estrogen-induced responses are substantially inhibited while other proteins not regulated by estrogens and cell growth are not affected by BrdUrd. This effect of BrdUrd is not secondary to a decrease in estrogen receptor levels and appears to require incorporation of BrdUrd into DNA for the following reasons. First, there is a lag before any effect of BrdUrd is seen which is similar to the doubling time of the cells. Second, the effect of BrdUrd is not seen when cells are cultured in medium containing BrdUrd and 1-beta-D-arabinofuranosylcytosine, a DNA synthesis inhibitor, or excess thymidine, which blocks the incorporation of BrdUrd into DNA. Finally 2'-deoxycytidine, which reverses the effects of non-incorporated BrdUrd, is without effect on the inhibition of the estrogen-induced 46 000-Mr protein. We conclude that BrdUrd selectively prevents the effects of estrogens in MCF7 cells and that the mechanism of this anti-estrogenic effect of BrdUrd probably requires its incorporation into DNA and occurs beyond the nuclear translocation step of the estrogen receptor. Alterations in the recognition of chromatin effector sites by the estrogen-receptor complex could be involved in preventing hormone action.
D001943:Breast Neoplasms / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002455:Cell Division; D002460:Cell Line; D004261:DNA Replication; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism
D009363:Neoplasm Proteins; D011980:Receptors, Progesterone; D004958:Estradiol; D001973:Bromodeoxyuridine