{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:19:51Z","timestamp":1777612791802,"version":"3.51.4"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T00:00:00Z","timestamp":1571356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Baltimore Veterans Affairs","award":["Merit Review"],"award-info":[{"award-number":["Merit Review"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The microtubule-stabilizing agent docetaxel in combination with gemcitabine represents one of the most effective regimens against the aggressive gynecologic tumor leiomyosarcoma (LMS). Upregulation of class III \u03b2-tubulin has previously been shown to confer taxane resistance in a variety of human cancers. Prostaglandin E2 receptor EP4 is linked to progression of a variety of human cancers and may represent a novel target for tumor inhibition in LMS. We evaluated the hypotheses that EP4 and class III \u03b2-tubulin have increased expression in LMS in comparison to normal myometrium or benign tumors and that expression of class III \u03b2-tubulin correlates with resistance to taxanes and poor clinical outcome. Gene expression was examined using TCGA data and correlated with clinicopathologic outcome which demonstrated that class III \u03b2-tubulin is more highly expressed in more aggressive sarcomas with EP4 being widely expressed in all subtypes of sarcoma. Immunohistochemistry for EP4 and class III \u03b2-tubulin was performed on patients with LMS, leiomyomatosis\/STUMP, leiomyoma, and normal myometrium. Expression of EP4 and class III \u03b2-tubulin were characterized for cell lines SK-UT-1, SK-UT-1B, and PHM-41 and these cell lines were treated with docetaxel alone and in combination with EP4 inhibitors. In taxane-resistant cell lines that overexpress class III \u03b2-tubulin and EP4, treatment with EP4 inhibitor resulted in at least 2-fold sensitization to docetaxel. Expression of class III \u03b2-tubulin and EP4 in LMS may identify patients at risk of resistance to standard chemotherapies and candidates for augmentation of therapy through EP4 inhibition.<\/jats:p>","DOI":"10.3390\/cancers11101590","type":"journal-article","created":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T11:24:15Z","timestamp":1571397855000},"page":"1590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["EP4 and Class III \u03b2-Tubulin Expression in Uterine Smooth Muscle Tumors: Implications for Prognosis and Treatment"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9971-9087","authenticated-orcid":false,"given":"Jocelyn","family":"Reader","sequence":"first","affiliation":[{"name":"Division of Gynecologic Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy K.","family":"Harper","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teklu","family":"Legesse","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-5750","authenticated-orcid":false,"given":"Paul N.","family":"Staats","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Goloubeva","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gautam G.","family":"Rao","sequence":"additional","affiliation":[{"name":"University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Fulton","sequence":"additional","affiliation":[{"name":"University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"},{"name":"Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7098-6376","authenticated-orcid":false,"given":"Dana M.","family":"Roque","sequence":"additional","affiliation":[{"name":"University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. 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