{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:31:12Z","timestamp":1790958672264,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T00:00:00Z","timestamp":1145577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:p>\n                    <jats:bold>Abstract:\u2002<\/jats:bold>\n                    Cadmium (Cd) is a heavy metal affecting human health both through environmental and occupational exposure. There is evidence that Cd accumulates in several organs and is carcinogenic to humans. In vivo, Cd mimics the effect of estrogens in the uterus and mammary gland. In estrogen\u2010responsive breast cancer cell lines, Cd stimulates proliferation and can also activate the estrogen receptor independent of estradiol. The ability of this metalloestrogen to increase gene expression in MCF7 cells is blocked by anti\u2010estrogens suggesting that the activity of these compounds is mediated by ER\n                    <jats:italic>\u03b1<\/jats:italic>\n                    . The aims of this work were to test whether melatonin inhibits Cd\u2010induced proliferation in MCF7 cells, and also to study whether melatonin specifically inhibits Cd\u2010induced ER\n                    <jats:italic>\u03b1<\/jats:italic>\n                    transactivation. We show that melatonin prevents the Cd\u2010induced growth of synchronized MCF7 breast cancer cells. In transient transfection experiments, we prove that both ER\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010 and ER\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010mediated transcription are stimulated by Cd. Melatonin is a specific inhibitor of Cd\u2010induced ER\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010mediated transcription in both estrogen response elements (ERE)\u2010 and AP1\u2010containing promoters, whereas ER\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010mediated transcription is not inhibited by the pineal indole. Moreover, the mutant ER\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010(K302G, K303G), unable to bind calmodulin, is activated by Cd but becomes insensitive to melatonin treatment. These results proved that melatonin inhibits MCF7 cell growth induced by Cd and abolishes the stimulatory effect of the heavy metal in cells expressing ER\n                    <jats:italic>\u03b1<\/jats:italic>\n                    at both ERE\u2010luc and AP1\u2010luc sites. We can infer from these experiments that melatonin regulates Cd\u2010induced transcription in both ERE\u2010 and AP1 pathways. These results also reinforce the hypothesis of the anti\u2010estrogenic properties of melatonin as a valuable tool in breast cancer therapies.\n                  <\/jats:p>","DOI":"10.1111\/j.1600-079x.2006.00315.x","type":"journal-article","created":{"date-parts":[[2006,1,25]],"date-time":"2006-01-25T04:22:38Z","timestamp":1138162958000},"page":"291-296","source":"Crossref","is-referenced-by-count":75,"title":["Melatonin inhibits both ER\u03b1 activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium"],"prefix":"10.1111","volume":"40","author":[{"given":"C.","family":"Mart\u00ednez\u2010Campa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Alonso\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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