{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:50:42Z","timestamp":1792443042591,"version":"4.5.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,5,27]]},"abstract":"<jats:p>\n                    Retinoic acid is one of the most promising drugs for chemotherapy and chemoprevention of cancer. Either blocking activator protein-1 (AP-1) activity or activating retinoic acid response element (RARE) have been proposed to be responsible for its antitumor activity. However, evidence for this hypothesis is lacking\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies. To address this issue, we used an AP-1-luciferase transgenic mouse as a carcinogenesis model and new synthetic retinoids that are either selective inhibitors of AP-1 activation or selective activators of the RARE. The results showed that the SR11302, an AP-1 inhibition-specific retinoid, and other AP-1 inhibitors such as trans-retinoic acid and fluocinolone acetonide, markedly inhibit both 12-\n                    <jats:italic>O<\/jats:italic>\n                    -tetradecanoylphorbol-13-acetate-induced papilloma formation and AP-1 activation in 7,12-dimethyl benz(a)anthracene-initiated mouse skin (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). In contrast, repeated applications of SR11235, a retinoid with RARE transactivating activity, but devoid of AP-1 inhibiting effect, did not cause significant inhibition of papilloma formation and AP-1 activation (\n                    <jats:italic>P<\/jats:italic>\n                    &gt; 0.05). These results provide the first\n                    <jats:italic>in vivo<\/jats:italic>\n                    evidence that the antitumor effect of retinoids is mediated by blocking AP-1 activity, but not by activation of RARE.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.11.5826","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:43:20Z","timestamp":1027680200000},"page":"5826-5830","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":194,"title":["Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic\u2009acid"],"prefix":"10.1073","volume":"94","author":[{"given":"Chuanshu","family":"Huang","sequence":"first","affiliation":[{"name":"The Hormel Institute, University of Minnesota, 801 16th Avenue, N.E., Austin, MN 55912; Retinoid Program, SRI International, Menlo Park, CA 94025; and Section of Immunology, Howard Hughes Medical Institute, Yale University School of Medicine, P.O. Box 3333, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Ya","family":"Ma","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, 801 16th Avenue, N.E., Austin, MN 55912; Retinoid Program, SRI International, Menlo Park, CA 94025; and Section of Immunology, Howard Hughes Medical Institute, Yale University School of Medicine, P.O. Box 3333, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia I.","family":"Dawson","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, 801 16th Avenue, N.E., Austin, MN 55912; Retinoid Program, SRI International, Menlo Park, CA 94025; and Section of Immunology, Howard Hughes Medical Institute, Yale University School of Medicine, P.O. Box 3333, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Rincon","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, 801 16th Avenue, N.E., Austin, MN 55912; Retinoid Program, SRI International, Menlo Park, CA 94025; and Section of Immunology, Howard Hughes Medical Institute, Yale University School of Medicine, P.O. Box 3333, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, 801 16th Avenue, N.E., Austin, MN 55912; Retinoid Program, SRI International, Menlo Park, CA 94025; and Section of Immunology, Howard Hughes Medical Institute, Yale University School of Medicine, P.O. Box 3333, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zigang","family":"Dong","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, 801 16th Avenue, N.E., Austin, MN 55912; Retinoid Program, SRI International, Menlo Park, CA 94025; and Section of Immunology, Howard Hughes Medical Institute, Yale University School of Medicine, P.O. Box 3333, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,5,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90611-8"},{"key":"e_1_3_3_2_2","first-page":"129","volume":"1072","author":"Angel P","year":"1991","unstructured":"P Angel, M Karin Biochim Biophys Acta 1072, 129\u2013157 (1991).","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.8.5.2063-2069.1988"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90147-X"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb03525.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90146-8"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.5.1500"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb03441.x"},{"key":"e_1_3_3_9_2","first-page":"6286","volume":"11","author":"Alani R","year":"1991","unstructured":"R Alani, P Brown, B Binetruy, H Dosaker, R K Rosenberg, P Angel, M Karin, M J Birrer Mol Cell Biol 11, 6286\u20136295 (1991).","journal-title":"Mol Cell Biol"},{"key":"e_1_3_3_10_2","first-page":"9","volume":"5","author":"Domann F E","year":"1994","unstructured":"F E Domann, J P Levy, M J Birrer, G T Bowden Cell Growth Differ 5, 9\u201316 (1994).","journal-title":"Cell Growth Differ"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.2.609"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/16.4.749"},{"key":"e_1_3_3_13_2","first-page":"359","volume":"7","author":"Dong Z G","year":"1995","unstructured":"Z G Dong, R G Watts, Y Sun, S N Zhan, N H Colburn Int J Oncol 7, 359\u2013364 (1995).","journal-title":"Int J Oncol"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.11.6427"},{"key":"e_1_3_3_15_2","first-page":"389","volume":"8","author":"Huang C S","year":"1996","unstructured":"C S Huang, W-Y Ma, Z G Dong Int J Oncol 8, 389\u2013393 (1996).","journal-title":"Int J Oncol"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940090202"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940050106"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.4.1402"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/15.6.1105"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06757.x"},{"key":"e_1_3_3_21_2","first-page":"483","volume":"56","author":"Li J-J","year":"1996","unstructured":"J-J Li, Z Dong, M I Dawson, N H Colburn Cancer Res 56, 483\u2013489 (1996).","journal-title":"Cancer Res"},{"key":"e_1_3_3_22_2","first-page":"655","volume":"3","author":"Gudas L J","year":"1992","unstructured":"L J Gudas Cell Growth Differ 3, 655\u2013662 (1992).","journal-title":"Cell Growth Differ"},{"key":"e_1_3_3_23_2","first-page":"3045","volume":"43","author":"Verma A K","year":"1983","unstructured":"A K Verma, C T Garcia, C L Ashendel, R K Boutwell Cancer Res 43, 3045\u20133049 (1983).","journal-title":"Cancer Res"},{"key":"e_1_3_3_24_2","first-page":"419","volume":"39","author":"Verma A K","year":"1979","unstructured":"A K Verma, B G Shapas, H M Rice, R K Boutwell Cancer Res 39, 419\u2013425 (1979).","journal-title":"Cancer Res"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/12.12.2325"},{"key":"e_1_3_3_26_2","first-page":"121","volume-title":"Early Detection of Cancer Molecular Markers","author":"Dong Z","year":"1994","unstructured":"Z Dong, N H Colburn Early Detection of Cancer Molecular Markers, eds S Srivastava, S M Lippman, W K Hong, J L Mulshine (Futura, Armonk, NY), pp. 121\u2013128 (1994)."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1992.10.5.839"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V72.2.567.567"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199009203231205"},{"key":"e_1_3_3_30_2","first-page":"13","volume":"35","author":"Bollag W","year":"1992","unstructured":"W Bollag, E E Holdener Ann Oncol 35, 13\u201326 (1992).","journal-title":"Ann Oncol"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/330624a0"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/333669a0"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.9.3559"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1335166"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/372107a0"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90395-U"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.14.6092"},{"key":"e_1_3_3_38_2","first-page":"597","volume-title":"The Retinoids: Biology, Chemistry, and Medicine","author":"Hong W K","year":"1994","unstructured":"W K Hong, L M Itri The Retinoids: Biology, Chemistry, and Medicine, eds M B Sporn, A B Roberts, D S Goodman (Raven, New York), pp. 597\u2013630 (1994)."},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/scel.1994.1015"},{"key":"e_1_3_3_40_2","first-page":"623","volume":"10","author":"Glass C K","year":"1991","unstructured":"C K Glass, J DiRenzo, R Kurokawa, Z Han Cell Biol 10, 623\u2013638 (1991).","journal-title":"Cell Biol"},{"key":"e_1_3_3_41_2","first-page":"319","volume-title":"The Retinoids","author":"Mangelsdorf D J","year":"1994","unstructured":"D J Mangelsdorf, K Umesono, R M Evans The Retinoids, eds M B Sporn, A B Roberts, D S Goodman (Academic, Orlando, FL), pp. 319\u2013349 (1994)."},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0083-6729(08)61150-4"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90479-V"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/355359a0"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.94.11.5826","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:29:24Z","timestamp":1649860164000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.94.11.5826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,5,27]]},"references-count":44,"journal-issue":{"issue":"11","published-print":{"date-parts":[[1997,5,27]]}},"alternative-id":["10.1073\/pnas.94.11.5826"],"URL":"https:\/\/doi.org\/10.1073\/pnas.94.11.5826","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,5,27]]},"assertion":[{"value":"1997-02-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1997-03-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1997-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}