{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:06:22Z","timestamp":1791201982291,"version":"4.2.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"8","license":[{"start":{"date-parts":[[2009,8,24]],"date-time":"2009-08-24T00:00:00Z","timestamp":1251072000000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,2,24]]},"abstract":"<jats:p>\n                    Lymphangioleiomyomatosis (LAM) is an often fatal disease primarily affecting young women in which tuberin (TSC2)-null cells metastasize to the lungs. The mechanisms underlying the striking female predominance of LAM are unknown. We report here that 17-\u03b2-estradiol (E\n                    <jats:sub>2<\/jats:sub>\n                    ) causes a 3- to 5-fold increase in pulmonary metastases in male and female mice, respectively, and a striking increase in circulating tumor cells in mice bearing tuberin-null xenograft tumors. E\n                    <jats:sub>2<\/jats:sub>\n                    -induced metastasis is associated with activation of p42\/44 MAPK and is completely inhibited by treatment with the MEK1\/2 inhibitor, CI-1040. In vitro, E\n                    <jats:sub>2<\/jats:sub>\n                    inhibits anoikis of tuberin-null cells. Finally, using a bioluminescence approach, we found that E\n                    <jats:sub>2<\/jats:sub>\n                    enhances the survival and lung colonization of intravenously injected tuberin-null cells by 3-fold, which is blocked by treatment with CI-1040. Taken together these results reveal a new model for LAM pathogenesis in which activation of MEK-dependent pathways by E\n                    <jats:sub>2<\/jats:sub>\n                    leads to pulmonary metastasis via enhanced survival of detached tuberin-null cells.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0810790106","type":"journal-article","created":{"date-parts":[[2009,2,7]],"date-time":"2009-02-07T04:03:42Z","timestamp":1233979422000},"page":"2635-2640","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":151,"title":["Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells"],"prefix":"10.1073","volume":"106","author":[{"given":"Jane J.","family":"Yu","sequence":"first","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria A.","family":"Robb","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasha A.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Ariazi","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Karbowniczek","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristotelis","family":"Astrinidis","sequence":"additional","affiliation":[{"name":"Drexel University College of Medicine, Philadelphia, PA 19102;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunrong","family":"Wang","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Hernandez-Cuebas","sequence":"additional","affiliation":[{"name":"Drexel University College of Medicine, Philadelphia, PA 19102;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura F.","family":"Seeholzer","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Nicolas","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey","family":"Hensley","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA 19111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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