{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:28:04Z","timestamp":1789810084926,"version":"4.0.1"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2002,2,6]],"date-time":"2002-02-06T00:00:00Z","timestamp":1012953600000},"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":[[2002,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Resistance to the antiestrogen tamoxifen is the main stumbling block for the success of breast cancer therapy. We focused our study on cellular alterations induced by a prolonged treatment with the active tamoxifen metabolite hydroxytamoxifen (OHT). We show that a prolonged OHT treatment (for up to 7 days) led to a progressive increase in the level of phosphorylated p44\/42 mitogen activated kinase (MAP kinase) induced by 10<jats:sup>\u22127<\/jats:sup> M TPA stimulation, without any significant change in the protein level. This effect was also observed in MCF\u20107 cells grown first in medium containing dextran\u2010coated charcoal\u2010treated FCS (DCC medium) for 20 days prior to OHT treatment, indicating a specific effect of the antiestrogen and not an effect of estrogen deprivation. It was prevented by cotreatment with estradiol and not observed in the estrogen receptor negative HeLa cell line, suggesting that it was mediated by the estrogen receptor. TPA induced phosphorylation of MEK1\/2 was also raised by OHT treatment, without any change in their protein level or Raf\u20101 and H\u2010Ras levels. When the MCF\u20107R OHT resistant cell line was grown in antiestrogen containing medium, the level of phosphorylated p44\/42 MAP kinase was also high but reversed when the antiestrogen was removed. The 2 other MAP kinase, JNK and P38 pathways were not affected in the same way by OHT treatment. In conclusion, our data reveal that a prolonged OHT treatment, by increasing p44\/42 MAPK activity, affects a key step in the growth control of MCF\u20107 cells, although not sufficiently to overcome the growth inhibitory effect of the drug. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10252","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:13:41Z","timestamp":1030317221000},"page":"698-706","source":"Crossref","is-referenced-by-count":12,"title":["Effect of prolonged hydroxytamoxifen treatment of MCF\u20107 cells on mitogen activated kinase cascade"],"prefix":"10.1002","volume":"98","author":[{"given":"Fanjaniriana","family":"Rabenoelina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhabib","family":"Semlali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Jos\u00e8phe","family":"Duchesne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Freiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Pons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Badia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,2,6]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00666205"},{"key":"e_1_2_6_3_2","first-page":"5860","article-title":"Hydroxytamoxifen induces a rapid and irreversible inactivation of an estrogenic response in an MCF\u20107\u2010derived cell line","volume":"54","author":"Badia E","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005801005966"},{"key":"e_1_2_6_5_2","first-page":"4130","article-title":"Long\u2010term hydroxytamoxifen treatment of an MCF\u20107\u2010derived breast cancer cell line irreversibly inhibits the expression of estrogenic genes through chromatin remodeling","volume":"60","author":"Badia E","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119309"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203032"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.47.31317"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.3.1032"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5241.1491"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.21.13317"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.8.4686"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1996.tb16234.x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00471.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.3.824"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90690-0"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201005"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.17.6612-6625.2000"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.14.11.1882"},{"key":"e_1_2_6_20_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1210\/mend.15.1.0590","article-title":"Potentiation of Estrogen Receptor Activation Function 1 (AF\u20101) by Src\/JNK through a Serine 118\u2010Independent Pathway","volume":"15","author":"Feng W","year":"2001","journal-title":"Mol Endocrinol"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012048626963"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.9.12.1804"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.9.3844"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(87)90819-9"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1660329"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.49.31163"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)80873-3"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.7.8259"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.1.7270"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006406030612"},{"key":"e_1_2_6_31_2","first-page":"4071","article-title":"Elevated mitogen\u2010activated protein kinase activity in estrogen\u2010nonresponsive human breast cancer cells","volume":"58","author":"Coutts AS","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106448200"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42250-2"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1515\/bchm.1997.378.9.1023"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1994.1120"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60765-4"},{"key":"e_1_2_6_37_2","first-page":"849","article-title":"Stress\u2010activated protein kinases bind directly to the delta domain of c\u2010Jun in resting cells: implications for repression of c\u2010Jun function","volume":"10","author":"Dai T","year":"1995","journal-title":"Oncogene"},{"key":"e_1_2_6_38_2","first-page":"251","article-title":"Increased activator protein\u20101 DNA binding and c\u2010Jun NH2\u2010terminal kinase activity in human breast tumors with acquired tamoxifen resistance","volume":"5","author":"Johnston SR","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.23.1926"},{"key":"e_1_2_6_40_2","first-page":"351","article-title":"Progression of MCF\u20107 breast cancer cells to antiestrogen\u2010resistant phenotype is accompanied by elevated levels of AP\u20101 DNA\u2010binding activity","volume":"7","author":"Dumont JA","year":"1996","journal-title":"Cell Growth Diff"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202989"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19970304)70:5<567::AID-IJC13>3.0.CO;2-A"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19980911)77:6<928::AID-IJC22>3.0.CO;2-W"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(98)00315-2"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.10252","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.10252","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T05:14:29Z","timestamp":1696914869000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.10252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,2,6]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2002,4,10]]}},"alternative-id":["10.1002\/ijc.10252"],"URL":"https:\/\/doi.org\/10.1002\/ijc.10252","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,2,6]]}}}