{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:28:09Z","timestamp":1764224889556},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,10,22]],"date-time":"2007-10-22T00:00:00Z","timestamp":1193011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multidrug resistance, the phenomenon by which cells treated with a drug become resistant to the cytotoxic effect of a variety of other structurally and functionally unrelated drugs, is often associated with the expression of P\u2010glycoprotein, an efflux membrane pump coded by the <jats:italic>MDR1 (ABCB1<\/jats:italic>) gene. Transcription from <jats:italic>MDR1<\/jats:italic> can start at 2 promoters: a well\u2010characterized downstream promoter and an as yet uncharacterized upstream promoter (USP). We have previously determined that the USP is activated in some drug\u2010resistant cell lines, in primary breast tumors and in metastatic epithelial cells isolated from the lymph nodes of breast cancer patients. In this study, we report the cloning and characterization of the <jats:italic>MDR1<\/jats:italic> USP and studied its association with chemotherapy response in breast cancer patients. Deletion analysis indicated that a nearby endogenous retroviral long terminal repeat is not responsible for promoter activation, and that the region within the first 400 nucleotides upstream from the transcription start point contained all the elements necessary for promoter activity in drug\u2010resistant cells. We identified an element recognized by the transcription factor NF\u2010IL6 (activated upon interleukin\u20106 exposure) which is necessary for promoter activity in drug\u2010resistant cells and plays a role in the activation of the promoter in response to interleukin\u20106 in breast cancer MCF\u20107 cells. Although transcripts from this promoter are associated with translating polyribosomes, their low abundance makes the amount of synthesized P\u2010glycoprotein insufficient to affect the response to first\u2010line chemotherapy in patients with advanced breast cancer. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23149","type":"journal-article","created":{"date-parts":[[2007,10,22]],"date-time":"2007-10-22T14:21:33Z","timestamp":1193062893000},"page":"1058-1067","source":"Crossref","is-referenced-by-count":18,"title":["Production of P\u2010glycoprotein from the <i>MDR1<\/i> upstream promoter is insufficient to affect the response to first\u2010line chemotherapy in advanced breast cancer"],"prefix":"10.1002","volume":"122","author":[{"given":"Selina","family":"Raguz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca A.","family":"Randle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva R.","family":"Sharpe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Foekens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anieta M.","family":"Sieuwerts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion E.","family":"Meijer\u2010van Gelder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junia V.","family":"Melo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher F.","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernesto","family":"Yag\u00fce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,12,24]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.53.082901.103929"},{"key":"e_1_2_5_3_2","first-page":"827","article-title":"RNA expression of breast cancer resistance protein, lung resistance\u2010related protein, multidrug resistance\u2010associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: correlation with chemotherapeutic response","volume":"9","author":"Burger H","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1984"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.58.1.1"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.66.2.268"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.65.4.906"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)75806-2"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)45397-5"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)40260-3"},{"key":"e_1_2_5_11_2","first-page":"117","article-title":"Transcription of the multidrug resistance gene MDR1: a therapeutic target","volume":"1","author":"Scotto KW","year":"2001","journal-title":"Mol Interv"},{"key":"e_1_2_5_12_2","first-page":"3377","article-title":"Ecteinascidin\u2010743 inhibits activated but not constitutive transcription","volume":"62","author":"Friedman D","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.7.4377"},{"key":"e_1_2_5_14_2","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1182\/blood.V74.4.1388.1388","article-title":"Expression of the mdr\u20101\/P\u2010170 gene in patients with acute lymphoblastic leukemia","volume":"74","author":"Rothenberg ML","year":"1989","journal-title":"Blood"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0517"},{"key":"e_1_2_5_16_2","first-page":"8851","article-title":"Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells","volume":"61","author":"Conze D","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_5_18_2","volume-title":"Molecular cloning. 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