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Hagemeister Research Fund"},{"name":"Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology in Japan"},{"name":"Japan Leukemia Research Fund"},{"name":"Osaka Cancer Research Foundation"},{"name":"Paul and Mary Haas Chair in Genetics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:p>The nuclear transporter exportin\u20101 (<jats:styled-content style=\"fixed-case\">XPO<\/jats:styled-content>1) is highly expressed in mantle cell lymphoma (<jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content>) cells, and is believed to be associated with the pathogenesis of this disease. <jats:styled-content style=\"fixed-case\">XPO<\/jats:styled-content>1\u2010selective inhibitors of nuclear export (<jats:styled-content style=\"fixed-case\">SINE<\/jats:styled-content>) compounds have been shown to induce apoptosis in <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cells. Given that p53 is a cargo protein of <jats:styled-content style=\"fixed-case\">XPO<\/jats:styled-content>1, we sought to determine the significance of p53 activation through <jats:styled-content style=\"fixed-case\">XPO<\/jats:styled-content>1 inhibition in <jats:styled-content style=\"fixed-case\">SINE<\/jats:styled-content>\u2010induced apoptosis of <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cells. We investigated the prognostic impact of <jats:styled-content style=\"fixed-case\">XPO<\/jats:styled-content>1 expression in <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cells using Oncomine analysis. The significance of p53 mutational\/functional status on sensitivity to <jats:styled-content style=\"fixed-case\">XPO<\/jats:styled-content>1 inhibition in cell models and primary <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> samples, and the functional role of p53\u2010mediated apoptosis signaling, were also examined. Increased <jats:styled-content style=\"fixed-case\">XPO<\/jats:styled-content>1 expression was associated with poor prognosis in <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> patients. The <jats:styled-content style=\"fixed-case\">XPO<\/jats:styled-content>1 inhibitor <jats:styled-content style=\"fixed-case\">KPT<\/jats:styled-content>\u2010185 induced apoptosis in <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cells through p53\u2010dependent and \u2010independent mechanisms, and p53 status was a critical determinant of its apoptosis induction. The <jats:styled-content style=\"fixed-case\">KPT<\/jats:styled-content>\u2010185\u2010induced, p53\u2010mediated apoptosis in the <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cells occurred in a transcription\u2010dependent manner. Exportin\u20101 appears to influence patient survival in <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content>, and the <jats:styled-content style=\"fixed-case\">SINE XPO<\/jats:styled-content>1 antagonist <jats:styled-content style=\"fixed-case\">KPT<\/jats:styled-content>\u2010185 effectively activates p53\u2010mediated transcription and apoptosis, which would provide a novel strategy for the therapy of <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cas.12430","type":"journal-article","created":{"date-parts":[[2014,4,26]],"date-time":"2014-04-26T04:59:20Z","timestamp":1398488360000},"page":"795-801","source":"Crossref","is-referenced-by-count":86,"title":["Induction of p53\u2010mediated transcription and apoptosis by exportin\u20101 (<scp>XPO<\/scp>1) inhibition in mantle cell lymphoma"],"prefix":"10.1111","volume":"105","author":[{"given":"Mariko","family":"Yoshimura","sequence":"first","affiliation":[{"name":"Hematology Respiratory Medicine and Oncology Department of Medicine Saga University Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Ishizawa","sequence":"additional","affiliation":[{"name":"Molecular Hematology and Therapy Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Ruvolo","sequence":"additional","affiliation":[{"name":"Molecular Hematology and Therapy Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Dilip","sequence":"additional","affiliation":[{"name":"Molecular Hematology and Therapy Department of Leukemia The University of Texas MD Anderson Cancer Center Houston 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