{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:59:36Z","timestamp":1771005576463,"version":"3.50.1"},"reference-count":55,"publisher":"Proceedings of the National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,4,10]]},"abstract":"<jats:p>\n            Mutations of the tumor suppressor PTEN, a phosphatase with\n specificity for 3-phosphorylated inositol phospholipids, accompany\n progression of brain tumors from benign to the most malignant forms.\n Tumor progression, particularly in aggressive and malignant tumors, is\n associated with the induction of angiogenesis, a process termed the\n angiogenic switch. Therefore, we tested whether PTEN regulates tumor\n progression by modulating angiogenesis. U87MG glioma cells stably\n reconstituted with PTEN cDNA were tested for growth in a nude mouse\n orthotopic brain tumor model. We observed that the reconstitution of\n wild-type PTEN had no effect on\n            <jats:italic>in vitro<\/jats:italic>\n            proliferation\n but dramatically decreased tumor growth\n            <jats:italic>in vivo<\/jats:italic>\n            and\n prolonged survival in mice implanted intracranially with these tumor\n cells. PTEN reconstitution diminished phosphorylation of AKT within the\n PTEN-reconstituted tumor, induced thrombospondin 1 expression, and\n suppressed angiogenic activity. These effects were not observed in\n tumors reconstituted with a lipid phosphatase inactive G129E mutant of\n PTEN, a result that provides evidence that the lipid phosphatase\n activity of PTEN regulates the angiogenic response\n            <jats:italic>in\n vivo<\/jats:italic>\n            . These data provide evidence that PTEN regulates\n tumor-induced angiogenesis and the progression of gliomas to a\n malignant phenotype via the regulation of phosphoinositide-dependent\n signals.\n          <\/jats:p>","DOI":"10.1073\/pnas.081063798","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:44:19Z","timestamp":1027694659000},"page":"4622-4627","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":193,"title":["PTEN controls tumor-induced angiogenesis"],"prefix":"10.1073","volume":"98","author":[{"given":"Shenghua","family":"Wen","sequence":"first","affiliation":[{"name":"Section of Hematology\/Oncology, Department of Pediatrics, Herman\r B Wells Center for Pediatric Research, Department of Biochemistry and\r Molecular Biology, Indiana School of Medicine, Indianapolis, IN 46202;\r and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY\r 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