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AKT Is Highly Phosphorylated in Pheochromocytomas But Not in Benign Adrenocortical Tumors
Context: Activation of AKT plays a major role in a variety of human neoplasias. In mice, a heterozygous deletion of the Pten gene is associated with increased activation of AKT and with development of pheochromocytomas. Objective: The objective of this study was the investigation of the role of AKT...
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| Published in: | The journal of clinical endocrinology and metabolism 2005-07, Vol.90 (7), p.4366-4370 |
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| container_end_page | 4370 |
| container_issue | 7 |
| container_start_page | 4366 |
| container_title | The journal of clinical endocrinology and metabolism |
| container_volume | 90 |
| creator | Fassnacht, Martin Weismann, Dirk Ebert, Silke Adam, Patrick Zink, Martina Beuschlein, Felix Hahner, Stefanie Allolio, Bruno |
| description | Context: Activation of AKT plays a major role in a variety of human neoplasias. In mice, a heterozygous deletion of the Pten gene is associated with increased activation of AKT and with development of pheochromocytomas.
Objective: The objective of this study was the investigation of the role of AKT in the pathogenesis of pheochromocytomas and adrenocortical tumors.
Design, Setting, and Participants: Total AKT and phosphorylated AKT (pAKT) in 15 pheochromocytomas, nine aldosterone-producing adenomas, nine cortisol-producing adenomas, eight adrenocortical carcinomas (ACC), and 15 normal adrenals were investigated by Western blot analysis. Immunohistochemistry for total AKT and pAKT was performed in pheochromocytomas (n = 8), ACC (n = 4), and normal adrenal glands (n = 2). In addition, in pheochromocytomas PTEN protein expression and PTEN loss of heterozygosity were analyzed.
Main Outcome Measures: Determination of pAKT/total AKT ratio in adrenal tissues was the main outcome.
Results: In comparison to normal adrenals, total AKT expression was elevated in both pheochromocytomas (193 ± 22%) and ACC (176 ± 36%). The pAKT/AKT ratio was significantly increased in pheochromocytomas (338 ± 49% vs. 100 ± 11%) but not in ACC, aldosterone-producing adenomas, and cortisol-producing adenomas. No loss of heterozygosity of PTEN and no decrease in PTEN protein was detected in pheochromocytomas. Immunohistochemistry showed strong and homogeneous AKT and pAKT staining in pheochromocytomas and focal staining in ACC.
Conclusion: Our findings provide evidence for increased activation of AKT in pheochromocytomas but not in adrenocortical adenomas. |
| doi_str_mv | 10.1210/jc.2004-2198 |
| format | article |
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Objective: The objective of this study was the investigation of the role of AKT in the pathogenesis of pheochromocytomas and adrenocortical tumors.
Design, Setting, and Participants: Total AKT and phosphorylated AKT (pAKT) in 15 pheochromocytomas, nine aldosterone-producing adenomas, nine cortisol-producing adenomas, eight adrenocortical carcinomas (ACC), and 15 normal adrenals were investigated by Western blot analysis. Immunohistochemistry for total AKT and pAKT was performed in pheochromocytomas (n = 8), ACC (n = 4), and normal adrenal glands (n = 2). In addition, in pheochromocytomas PTEN protein expression and PTEN loss of heterozygosity were analyzed.
Main Outcome Measures: Determination of pAKT/total AKT ratio in adrenal tissues was the main outcome.
Results: In comparison to normal adrenals, total AKT expression was elevated in both pheochromocytomas (193 ± 22%) and ACC (176 ± 36%). The pAKT/AKT ratio was significantly increased in pheochromocytomas (338 ± 49% vs. 100 ± 11%) but not in ACC, aldosterone-producing adenomas, and cortisol-producing adenomas. No loss of heterozygosity of PTEN and no decrease in PTEN protein was detected in pheochromocytomas. Immunohistochemistry showed strong and homogeneous AKT and pAKT staining in pheochromocytomas and focal staining in ACC.
Conclusion: Our findings provide evidence for increased activation of AKT in pheochromocytomas but not in adrenocortical adenomas.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2004-2198</identifier><identifier>PMID: 15855265</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Adrenal Cortex Neoplasms - metabolism ; Adrenal Gland Neoplasms - metabolism ; Adrenals. Adrenal axis. Renin-angiotensin system (diseases) ; Adult ; Aged ; Biological and medical sciences ; Endocrinopathies ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Immunohistochemistry ; Male ; Medical sciences ; Middle Aged ; Non tumoral diseases. Target tissue resistance. Benign neoplasms ; Pheochromocytoma - metabolism ; Phosphatidylinositol 3-Kinases - physiology ; Phosphoric Monoester Hydrolases - analysis ; Phosphorylation ; Protein-Serine-Threonine Kinases - metabolism ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-akt ; PTEN Phosphohydrolase ; Tumor Suppressor Proteins - analysis ; Vertebrates: endocrinology</subject><ispartof>The journal of clinical endocrinology and metabolism, 2005-07, Vol.90 (7), p.4366-4370</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-f9cdd2d046ac02ea6fc0de96b9b3f6b79414d6269cf2f4725485a20f54f2650c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16935768$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15855265$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fassnacht, Martin</creatorcontrib><creatorcontrib>Weismann, Dirk</creatorcontrib><creatorcontrib>Ebert, Silke</creatorcontrib><creatorcontrib>Adam, Patrick</creatorcontrib><creatorcontrib>Zink, Martina</creatorcontrib><creatorcontrib>Beuschlein, Felix</creatorcontrib><creatorcontrib>Hahner, Stefanie</creatorcontrib><creatorcontrib>Allolio, Bruno</creatorcontrib><title>AKT Is Highly Phosphorylated in Pheochromocytomas But Not in Benign Adrenocortical Tumors</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context: Activation of AKT plays a major role in a variety of human neoplasias. In mice, a heterozygous deletion of the Pten gene is associated with increased activation of AKT and with development of pheochromocytomas.
Objective: The objective of this study was the investigation of the role of AKT in the pathogenesis of pheochromocytomas and adrenocortical tumors.
Design, Setting, and Participants: Total AKT and phosphorylated AKT (pAKT) in 15 pheochromocytomas, nine aldosterone-producing adenomas, nine cortisol-producing adenomas, eight adrenocortical carcinomas (ACC), and 15 normal adrenals were investigated by Western blot analysis. Immunohistochemistry for total AKT and pAKT was performed in pheochromocytomas (n = 8), ACC (n = 4), and normal adrenal glands (n = 2). In addition, in pheochromocytomas PTEN protein expression and PTEN loss of heterozygosity were analyzed.
Main Outcome Measures: Determination of pAKT/total AKT ratio in adrenal tissues was the main outcome.
Results: In comparison to normal adrenals, total AKT expression was elevated in both pheochromocytomas (193 ± 22%) and ACC (176 ± 36%). The pAKT/AKT ratio was significantly increased in pheochromocytomas (338 ± 49% vs. 100 ± 11%) but not in ACC, aldosterone-producing adenomas, and cortisol-producing adenomas. No loss of heterozygosity of PTEN and no decrease in PTEN protein was detected in pheochromocytomas. Immunohistochemistry showed strong and homogeneous AKT and pAKT staining in pheochromocytomas and focal staining in ACC.
Conclusion: Our findings provide evidence for increased activation of AKT in pheochromocytomas but not in adrenocortical adenomas.</description><subject>Adrenal Cortex Neoplasms - metabolism</subject><subject>Adrenal Gland Neoplasms - metabolism</subject><subject>Adrenals. Adrenal axis. Renin-angiotensin system (diseases)</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Endocrinopathies</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Non tumoral diseases. Target tissue resistance. Benign neoplasms</subject><subject>Pheochromocytoma - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - physiology</subject><subject>Phosphoric Monoester Hydrolases - analysis</subject><subject>Phosphorylation</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>Tumor Suppressor Proteins - analysis</subject><subject>Vertebrates: endocrinology</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNptkD1PwzAQhi0EoqWwMaMsMJFiO7ZTj20FtKIChiLBZLn-aFMldrGTof-eRK3UheF00t2j93QPALcIDhFG8GmrhhhCkmLER2egjzihaY54fg76EGKU8hx_98BVjFsIESE0uwQ9REeUYkb74Gf8tkzmMZkV6025Tz43Pu42PuxLWRudFK6dGK82wVde7WtfyZhMmjp593W3nBhXrF0y1sE4r3yoCyXLZNlUPsRrcGFlGc3NsQ_A18vzcjpLFx-v8-l4kSoCUZ1arrTGGhImFcRGMqugNpyt-CqzbJVzgohmmHFlsSU5pmREJYaWEts-AFU2AA-H3F3wv42JtaiKqExZSmd8EwUbQYTaasHHA6iCjzEYK3ahqGTYCwRFp1JslehUik5li98dc5tVZfQJPrprgfsjIGP7tg3SqSKeOMYzmrMuKDtwxmmvQuHMLpgYxdY3wbVm_j__B82XjPw</recordid><startdate>20050701</startdate><enddate>20050701</enddate><creator>Fassnacht, Martin</creator><creator>Weismann, Dirk</creator><creator>Ebert, Silke</creator><creator>Adam, Patrick</creator><creator>Zink, Martina</creator><creator>Beuschlein, Felix</creator><creator>Hahner, Stefanie</creator><creator>Allolio, Bruno</creator><general>Endocrine Society</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20050701</creationdate><title>AKT Is Highly Phosphorylated in Pheochromocytomas But Not in Benign Adrenocortical Tumors</title><author>Fassnacht, Martin ; Weismann, Dirk ; Ebert, Silke ; Adam, Patrick ; Zink, Martina ; Beuschlein, Felix ; Hahner, Stefanie ; Allolio, Bruno</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-f9cdd2d046ac02ea6fc0de96b9b3f6b79414d6269cf2f4725485a20f54f2650c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adrenal Cortex Neoplasms - metabolism</topic><topic>Adrenal Gland Neoplasms - metabolism</topic><topic>Adrenals. Adrenal axis. Renin-angiotensin system (diseases)</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Endocrinopathies</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Non tumoral diseases. Target tissue resistance. Benign neoplasms</topic><topic>Pheochromocytoma - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - physiology</topic><topic>Phosphoric Monoester Hydrolases - analysis</topic><topic>Phosphorylation</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-akt</topic><topic>PTEN Phosphohydrolase</topic><topic>Tumor Suppressor Proteins - analysis</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fassnacht, Martin</creatorcontrib><creatorcontrib>Weismann, Dirk</creatorcontrib><creatorcontrib>Ebert, Silke</creatorcontrib><creatorcontrib>Adam, Patrick</creatorcontrib><creatorcontrib>Zink, Martina</creatorcontrib><creatorcontrib>Beuschlein, Felix</creatorcontrib><creatorcontrib>Hahner, Stefanie</creatorcontrib><creatorcontrib>Allolio, Bruno</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fassnacht, Martin</au><au>Weismann, Dirk</au><au>Ebert, Silke</au><au>Adam, Patrick</au><au>Zink, Martina</au><au>Beuschlein, Felix</au><au>Hahner, Stefanie</au><au>Allolio, Bruno</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AKT Is Highly Phosphorylated in Pheochromocytomas But Not in Benign Adrenocortical Tumors</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2005-07-01</date><risdate>2005</risdate><volume>90</volume><issue>7</issue><spage>4366</spage><epage>4370</epage><pages>4366-4370</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Context: Activation of AKT plays a major role in a variety of human neoplasias. In mice, a heterozygous deletion of the Pten gene is associated with increased activation of AKT and with development of pheochromocytomas.
Objective: The objective of this study was the investigation of the role of AKT in the pathogenesis of pheochromocytomas and adrenocortical tumors.
Design, Setting, and Participants: Total AKT and phosphorylated AKT (pAKT) in 15 pheochromocytomas, nine aldosterone-producing adenomas, nine cortisol-producing adenomas, eight adrenocortical carcinomas (ACC), and 15 normal adrenals were investigated by Western blot analysis. Immunohistochemistry for total AKT and pAKT was performed in pheochromocytomas (n = 8), ACC (n = 4), and normal adrenal glands (n = 2). In addition, in pheochromocytomas PTEN protein expression and PTEN loss of heterozygosity were analyzed.
Main Outcome Measures: Determination of pAKT/total AKT ratio in adrenal tissues was the main outcome.
Results: In comparison to normal adrenals, total AKT expression was elevated in both pheochromocytomas (193 ± 22%) and ACC (176 ± 36%). The pAKT/AKT ratio was significantly increased in pheochromocytomas (338 ± 49% vs. 100 ± 11%) but not in ACC, aldosterone-producing adenomas, and cortisol-producing adenomas. No loss of heterozygosity of PTEN and no decrease in PTEN protein was detected in pheochromocytomas. Immunohistochemistry showed strong and homogeneous AKT and pAKT staining in pheochromocytomas and focal staining in ACC.
Conclusion: Our findings provide evidence for increased activation of AKT in pheochromocytomas but not in adrenocortical adenomas.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>15855265</pmid><doi>10.1210/jc.2004-2198</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adrenal Cortex Neoplasms - metabolism Adrenal Gland Neoplasms - metabolism Adrenals. Adrenal axis. Renin-angiotensin system (diseases) Adult Aged Biological and medical sciences Endocrinopathies Female Fundamental and applied biological sciences. Psychology Humans Immunohistochemistry Male Medical sciences Middle Aged Non tumoral diseases. Target tissue resistance. Benign neoplasms Pheochromocytoma - metabolism Phosphatidylinositol 3-Kinases - physiology Phosphoric Monoester Hydrolases - analysis Phosphorylation Protein-Serine-Threonine Kinases - metabolism Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-akt PTEN Phosphohydrolase Tumor Suppressor Proteins - analysis Vertebrates: endocrinology |
| title | AKT Is Highly Phosphorylated in Pheochromocytomas But Not in Benign Adrenocortical Tumors |
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