Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2
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 Pten and Tsc2 act synergistically to suppress the severity of a subset of tumors specific to loss of each of these genes. I...
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| Veröffentlicht in: | Genes & development 2005-08, Vol.19 (15), p.1773-1778 |
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| container_title | Genes & development |
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| creator | Manning, Brendan D Logsdon, M Nicole Lipovsky, Alex I Abbott, Derek Kwiatkowski, David J Cantley, Lewis C |
| description | 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 Pten and Tsc2 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 Tsc2+/- mice exhibit defects in signaling downstream of Akt. However, Pten 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. |
| doi_str_mv | 10.1101/gad.1314605 |
| format | Article |
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This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature.</description><subject>Animals</subject><subject>Cell Division</subject><subject>Cell Line, Tumor</subject><subject>Feedback</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Phosphoric Monoester Hydrolases - genetics</subject><subject>Phosphoric Monoester Hydrolases - physiology</subject><subject>Polymerase Chain Reaction</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-akt</subject><subject>PTEN Phosphohydrolase</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - physiology</subject><subject>Research Communications</subject><subject>Signal Transduction</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - physiology</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkb1v3DAMxYWiQe-SdupeeOpSOCEtmbKWAoeg-QASZElmQZZln3q2dbV0CfLfx4cc2nTKQg7vx0cSj7GvCKeIgGedaU6RoyAoP7AllkLlpZDyI1tCpSBXnNSCHcf4GwAIiD6xBRIUEkkt2e2Fc01t7Cbz49rXPvkwZqHNVpuURd-Npvdjl_V-8Clmae2ybgpPab1H0m4IU8z6eXjP3EdbfGZHremj-3LoJ-zh4tf9-VV-c3d5fb66ya2QlPLClWCpIjlXzl1bFVxJwUtb8loANzjLhbJEIKBAIbDmhhpVyBqpbSTwE_bz1Xe7qwfXWDemyfR6O_nBTM86GK__V0a_1l141IjzLq5mg-8Hgyn82bmY9OCjdX1vRhd2UVMleEVF-S6IUoASFc3gj1fQTiHGybV_r0HQ-5z0nJM-5DTT394-8I89BMNfALVrjTM</recordid><startdate>20050801</startdate><enddate>20050801</enddate><creator>Manning, Brendan D</creator><creator>Logsdon, M Nicole</creator><creator>Lipovsky, Alex I</creator><creator>Abbott, Derek</creator><creator>Kwiatkowski, David J</creator><creator>Cantley, Lewis C</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20050801</creationdate><title>Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2</title><author>Manning, Brendan D ; 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Cell Division Cell Line, Tumor Feedback Humans Mice Mice, Inbred C57BL Mice, Knockout Phosphoric Monoester Hydrolases - genetics Phosphoric Monoester Hydrolases - physiology Polymerase Chain Reaction Protein-Serine-Threonine Kinases - metabolism Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-akt PTEN Phosphohydrolase Repressor Proteins - genetics Repressor Proteins - physiology Research Communications Signal Transduction Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - physiology |
| title | Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2 |
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