{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:06:47Z","timestamp":1792822007635,"version":"4.5.0"},"reference-count":39,"publisher":"Cold Spring Harbor Laboratory","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[2005,8,1]]},"abstract":"<jats:p>The PTEN and TSC2 tumor suppressors inhibit mammalian target of rapamycin (mTOR) signaling and are defective in distinct hamartoma syndromes. Using mouse genetics, we find that <jats:italic>Pten<\/jats:italic> and <jats:italic>Tsc2<\/jats:italic> act synergistically to suppress the severity of a subset of tumors specific to loss of each of these genes. Interestingly, we find that the slow-growing tumors specific to <jats:italic>Tsc2<\/jats:italic><jats:sup>+\/-<\/jats:sup> mice exhibit defects in signaling downstream of Akt. However, <jats:italic>Pten<\/jats:italic> haploinsufficiency restores Akt signaling in these tumors and dramatically enhances their severity. This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature.<\/jats:p>","DOI":"10.1101\/gad.1314605","type":"journal-article","created":{"date-parts":[[2005,7,19]],"date-time":"2005-07-19T00:24:43Z","timestamp":1121732683000},"page":"1773-1778","source":"Crossref","is-referenced-by-count":211,"title":["Feedback inhibition of Akt signaling limits the growth of tumors lacking <i>Tsc2<\/i>"],"prefix":"10.1101","volume":"19","author":[{"given":"Brendan D.","family":"Manning","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Nicole","family":"Logsdon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex I.","family":"Lipovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Abbott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Kwiatkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis C.","family":"Cantley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2005,7,18]]},"reference":[{"key":"2021111607300525000_19.15.1773.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.011528498"},{"key":"2021111607300525000_19.15.1773.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.8.4240"},{"key":"2021111607300525000_19.15.1773.3","doi-asserted-by":"publisher","DOI":"10.1038\/1235"},{"key":"2021111607300525000_19.15.1773.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5436.2122"},{"key":"2021111607300525000_19.15.1773.5","doi-asserted-by":"publisher","DOI":"10.1038\/84879"},{"key":"2021111607300525000_19.15.1773.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13044-9"},{"key":"2021111607300525000_19.15.1773.7","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3840"},{"key":"2021111607300525000_19.15.1773.8","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10257"},{"key":"2021111607300525000_19.15.1773.9","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207542"},{"key":"2021111607300525000_19.15.1773.10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202678200"},{"key":"2021111607300525000_19.15.1773.11","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200403069"},{"key":"2021111607300525000_19.15.1773.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-004-1795-3"},{"key":"2021111607300525000_19.15.1773.13","doi-asserted-by":"publisher","DOI":"10.1038\/ncb839"},{"key":"2021111607300525000_19.15.1773.14","first-page":"5645","volume":"62","year":"2002","journal-title":"Cancer Res."},{"key":"2021111607300525000_19.15.1773.15","first-page":"1206","volume":"59","year":"1999","journal-title":"Cancer Res."},{"key":"2021111607300525000_19.15.1773.16","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-1809.2003.00012.x"},{"key":"2021111607300525000_19.15.1773.17","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.5.525"},{"key":"2021111607300525000_19.15.1773.18","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20118"},{"key":"2021111607300525000_19.15.1773.19","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5308.1943"},{"key":"2021111607300525000_19.15.1773.20","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2002.1115"},{"key":"2021111607300525000_19.15.1773.21","doi-asserted-by":"crossref","unstructured":"Ma L ., Teruya-Feldstein, J., Behrendt, N., Chen, Z., Noda, T., Hino, O., Cordon-Cardo, C., and Pandolfi, P.P. 2005. Genetic analysis of Pten and Tsc2 functional interactions in the mouse reveals asymmetrical haploinsufficiency in tumor suppression. Genes & Dev. (this issue).","DOI":"10.1101\/gad.1314405"},{"key":"2021111607300525000_19.15.1773.22","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200408161"},{"key":"2021111607300525000_19.15.1773.23","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00568-3"},{"key":"2021111607300525000_19.15.1773.24","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600218"},{"key":"2021111607300525000_19.15.1773.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.171076798"},{"key":"2021111607300525000_19.15.1773.26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7319"},{"key":"2021111607300525000_19.15.1773.27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M213069200"},{"key":"2021111607300525000_19.15.1773.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.4.1563"},{"key":"2021111607300525000_19.15.1773.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.171060098"},{"key":"2021111607300525000_19.15.1773.30","doi-asserted-by":"publisher","DOI":"10.1038\/ncb840"},{"key":"2021111607300525000_19.15.1773.31","doi-asserted-by":"publisher","DOI":"10.1101\/gad.239102"},{"key":"2021111607300525000_19.15.1773.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.08.026"},{"key":"2021111607300525000_19.15.1773.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2004.06.007"},{"key":"2021111607300525000_19.15.1773.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81780-8"},{"key":"2021111607300525000_19.15.1773.35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6199"},{"key":"2021111607300525000_19.15.1773.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(07)00488-5"},{"key":"2021111607300525000_19.15.1773.37","first-page":"RE5","volume":"2003","year":"2003","journal-title":"Sci. STKE"},{"key":"2021111607300525000_19.15.1773.38","doi-asserted-by":"publisher","DOI":"10.1038\/nature02369"},{"key":"2021111607300525000_19.15.1773.39","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200317222"}],"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad.1314605","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T15:31:32Z","timestamp":1637076692000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad.1314605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,7,18]]},"references-count":39,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2005,8,1]]}},"alternative-id":["10.1101\/gad.1314605"],"URL":"https:\/\/doi.org\/10.1101\/gad.1314605","relation":{},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,7,18]]}}}