{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:58:56Z","timestamp":1773010736100,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Found in as many as 80% of women, uterine leiomyomas are a frequent cause of abnormal uterine bleeding, pelvic pain, and infertility. Despite their significant clinical impact, the mechanisms responsible for driving leiomyoma growth remain poorly understood. After obtaining IRB permission, expression of ecto\u20105\u2032\u2010nucleotidase (\n                    <jats:italic>NT5E,<\/jats:italic>\n                    CD73\n                    <jats:italic>)<\/jats:italic>\n                    was assessed in matched specimens of myometrium and leiomyoma by real\u2010time qPCR, Western blot, and immunohistochemistry (IHC). Adenosine concentrations were measured by enzyme\u2010linked assay. Primary cultures were used to assess the impact of adenosine and\/or adenosine receptor agonists on proliferation, apoptosis, and patterns of intracellular signaling in\u00a0vitro. When compared to matched specimens of healthy myometrium, uterine leiomyomas were characterized by reduced CD73 expression. Largely limited to thin\u2010walled vascular structures and the pseudocapsule of leiomyomas despite diffuse myometrial distribution. Restricted intra\u2010tumoral CD73 expression was accompanied by decreased levels of intra\u2010tumoral adenosine. In\u00a0vitro, incubation of primary leiomyoma cultures with adenosine or its hydrolysis\u2010resistant analog 2\u2010chloro\u2010adenosine (2\u2010CL\u2010AD) inhibited proliferation, induced apoptosis, and reduced proportion of myocytes in S\u2010 and G2\u2010M phases of the cell cycle. Decreased proliferation was accompanied by reduced expression of phospho\u2010Akt, phospho\u2010Cdk2\u2010Tyr15, and phospho\u2010Histone H3. Enforced expression of the A2B adenosine receptor (ADORA2B) and ADORA2B\u2010selective agonists similarly suppressed proliferation and inhibited Akt phosphorylation. Collectively, these observations broadly implicate CD73 and reduced\u00a0extracellular concentrations of\u00a0adenosine as key regulators of leiomyoma growth and potentially\u00a0identify novel strategies for clinically managing these common tumors.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401432r","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T01:44:56Z","timestamp":1727833496000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Spatially restricted ecto\u20105\u2032\u2010nucleotidase expression promotes the growth of uterine leiomyomas by modulating Akt activity"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9780-6339","authenticated-orcid":false,"given":"Xiaofang","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology University of South Florida Morsani College of Medicine  Tampa 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