Akt1 deficiency delays tumor progression, vascular invasion, and distant metastasis in a murine model of thyroid cancer
Akt activation is common in progressive thyroid cancer. In breast cancer, Akt1 induces primary cancer growth, but is reported to inhibit metastasis in vivo in several model systems. In contrast, clinical and in vitro studies suggest a metastasis-promoting role for Akt1 in thyroid cancer. The goal of...
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| Veröffentlicht in: | Oncogene 2011-10, Vol.30 (42), p.4307-4315 |
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| creator | Saji, M Narahara, K McCarty, S K Vasko, V V La Perle, K M Porter, K Jarjoura, D Lu, C Cheng, S-Y Ringel, M D |
| description | Akt activation is common in progressive thyroid cancer. In breast cancer, Akt1 induces primary cancer growth, but is reported to inhibit metastasis
in vivo
in several model systems. In contrast, clinical and
in vitro
studies suggest a metastasis-promoting role for Akt1 in thyroid cancer. The goal of this study was to determine the functional role of Akt1 in thyroid cancer growth and metastatic progression
in vivo
using thyroid hormone receptor (TR) β
PV/PV
knock-in (PV) mice, which develop metastatic thyroid cancer. We crossed Akt1
−/−
and PV mice and compared tumor development, local progression, metastasis and histology in
TRβ
PV/PV
/Akt1
+/+
(PVPV-Akt1WT) and
TRβ
PV/PV
/Akt1
−/−
(PVPV-Akt1KO) mice. Mice were killed at 3, 6, 9, 12 and 15 months; necropsy was performed and serum thyroid stimulating hormone (TSH) was measured. Thyroid hyperplasia occurred in both groups beginning at 3 months; the thyroid size was greater in the PVPV-Akt1WT mice (
P |
| doi_str_mv | 10.1038/onc.2011.136 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_900626556</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A271512848</galeid><sourcerecordid>A271512848</sourcerecordid><originalsourceid>FETCH-LOGICAL-c551t-a900712fa759edddb1e1c9f20ef459ad9223635d52117b8f8e26cc6b4aec1f033</originalsourceid><addsrcrecordid>eNp9kstv1DAQxiMEotvCjTOyQBUcmsXvxMdVxUuqxAXOltePxSWxi52A9r9nwi5UoIJ88Gj88zczmq9pnhC8Jpj1r3Kya4oJWRMm7zUrwjvZCqH4_WaFlcCtooyeNKe1XmOMO4Xpw-aEEsGoJHLVfN98mQhyPkQbfbJ7CAezr2iax1zQTcm74muNOV2gb6baeTAFxQThz5RJDrlYJ5MmNPrJQFRjBQAZNM4lJo_GDIooBzR93pccHbImWV8eNQ-CGap_fLzPmk9vXn-8fNdefXj7_nJz1VohyNQaBT0TGkwnlHfObYknVgWKfeBCGacoZZIJJygh3bYPvafSWrnlxlsSMGNnzYuDLozydfZ10mOs1g-DST7PVYO-pFIICeTL_5IE475nXLBF9Nlf6HWeS4I5dK8UJbTnHKDn_4Ko5IRjdpA6UjszeB1TyFMxdqmsN7QjYtHqgVrfQcFxfow2J1gf5P_4cHH4YEuutfigb0ocTdnDGHqxjQbb6MU2GmwD-NNjr_N29O43_MsnAJwfATCBGUKBJcZ6y_GO9lItddsDV-Ep7Xy5HfrOwj8Aee_XQg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2641403533</pqid></control><display><type>article</type><title>Akt1 deficiency delays tumor progression, vascular invasion, and distant metastasis in a murine model of thyroid cancer</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Nature Journals Online</source><source>SpringerLink Journals - AutoHoldings</source><creator>Saji, M ; Narahara, K ; McCarty, S K ; Vasko, V V ; La Perle, K M ; Porter, K ; Jarjoura, D ; Lu, C ; Cheng, S-Y ; Ringel, M D</creator><creatorcontrib>Saji, M ; Narahara, K ; McCarty, S K ; Vasko, V V ; La Perle, K M ; Porter, K ; Jarjoura, D ; Lu, C ; Cheng, S-Y ; Ringel, M D</creatorcontrib><description>Akt activation is common in progressive thyroid cancer. In breast cancer, Akt1 induces primary cancer growth, but is reported to inhibit metastasis
in vivo
in several model systems. In contrast, clinical and
in vitro
studies suggest a metastasis-promoting role for Akt1 in thyroid cancer. The goal of this study was to determine the functional role of Akt1 in thyroid cancer growth and metastatic progression
in vivo
using thyroid hormone receptor (TR) β
PV/PV
knock-in (PV) mice, which develop metastatic thyroid cancer. We crossed Akt1
−/−
and PV mice and compared tumor development, local progression, metastasis and histology in
TRβ
PV/PV
/Akt1
+/+
(PVPV-Akt1WT) and
TRβ
PV/PV
/Akt1
−/−
(PVPV-Akt1KO) mice. Mice were killed at 3, 6, 9, 12 and 15 months; necropsy was performed and serum thyroid stimulating hormone (TSH) was measured. Thyroid hyperplasia occurred in both groups beginning at 3 months; the thyroid size was greater in the PVPV-Akt1WT mice (
P
<0.001). In comparison with PVPV-Akt1WT mice, thyroid cancer development was delayed in the PVPV-Akt1KO mice (
P
=0.003) and the degree of tumor invasiveness was reduced. The PVPV-Akt1WT mice displayed pulmonary metastases at 12 and 15 months of age, by contrast PVPV-Akt1KO mice did not develop distant metastases at 15 months of age. Despite continued expression of Akt2 or Akt3, pAkt levels were decreased and there was evidence of reduced Akt effect on p27 in the PVPV-Akt1KO thyroids. TSH levels were similarly elevated in PV mice regardless of Akt1 expression. In conclusion, thyroid cancer development and progression in TR β
PV/PV
mice are Akt1-dependent, consistent with a tumor progression-promoting role in this murine thyroid cancer model.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2011.136</identifier><identifier>PMID: 21532616</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/322 ; 692/699/67/1459/1843 ; Adenoma - blood supply ; Adenoma - enzymology ; Age ; AKT protein ; AKT1 protein ; AKT2 protein ; Animal models ; Animals ; Apoptosis ; Autopsy ; Biological and medical sciences ; Breast cancer ; Carcinoma - blood supply ; Carcinoma - enzymology ; Carcinoma - secondary ; Cell Biology ; Cell physiology ; Cell receptors ; Cell structures and functions ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cellular biology ; Development and progression ; Endocrinopathies ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Knock-In Techniques ; Hormone receptors ; Hormones ; Human Genetics ; Hyperplasia ; Internal Medicine ; Invasiveness ; Kinases ; Lung ; Lung Neoplasms - secondary ; Malignant tumors ; Medical sciences ; Medicine ; Medicine & Public Health ; Metastases ; Metastasis ; Mice ; Mice, Inbred C57BL ; Miscellaneous ; Molecular and cellular biology ; Necropsy ; Neovascularization, Pathologic - enzymology ; Oncology ; original-article ; Physiological aspects ; Protein kinases ; Proto-Oncogene Proteins c-akt - deficiency ; Proto-Oncogene Proteins c-akt - metabolism ; Rodents ; Thyroid cancer ; Thyroid hormone receptors ; Thyroid Neoplasms - blood supply ; Thyroid Neoplasms - enzymology ; Thyroid Neoplasms - pathology ; Thyroid-stimulating hormone ; Thyroid. Thyroid axis (diseases) ; Thyrotropin - blood ; Tumors</subject><ispartof>Oncogene, 2011-10, Vol.30 (42), p.4307-4315</ispartof><rights>Macmillan Publishers Limited 2011</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2011.</rights><rights>Copyright Nature Publishing Group Oct 20, 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551t-a900712fa759edddb1e1c9f20ef459ad9223635d52117b8f8e26cc6b4aec1f033</citedby><cites>FETCH-LOGICAL-c551t-a900712fa759edddb1e1c9f20ef459ad9223635d52117b8f8e26cc6b4aec1f033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2011.136$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2011.136$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24728698$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21532616$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saji, M</creatorcontrib><creatorcontrib>Narahara, K</creatorcontrib><creatorcontrib>McCarty, S K</creatorcontrib><creatorcontrib>Vasko, V V</creatorcontrib><creatorcontrib>La Perle, K M</creatorcontrib><creatorcontrib>Porter, K</creatorcontrib><creatorcontrib>Jarjoura, D</creatorcontrib><creatorcontrib>Lu, C</creatorcontrib><creatorcontrib>Cheng, S-Y</creatorcontrib><creatorcontrib>Ringel, M D</creatorcontrib><title>Akt1 deficiency delays tumor progression, vascular invasion, and distant metastasis in a murine model of thyroid cancer</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Akt activation is common in progressive thyroid cancer. In breast cancer, Akt1 induces primary cancer growth, but is reported to inhibit metastasis
in vivo
in several model systems. In contrast, clinical and
in vitro
studies suggest a metastasis-promoting role for Akt1 in thyroid cancer. The goal of this study was to determine the functional role of Akt1 in thyroid cancer growth and metastatic progression
in vivo
using thyroid hormone receptor (TR) β
PV/PV
knock-in (PV) mice, which develop metastatic thyroid cancer. We crossed Akt1
−/−
and PV mice and compared tumor development, local progression, metastasis and histology in
TRβ
PV/PV
/Akt1
+/+
(PVPV-Akt1WT) and
TRβ
PV/PV
/Akt1
−/−
(PVPV-Akt1KO) mice. Mice were killed at 3, 6, 9, 12 and 15 months; necropsy was performed and serum thyroid stimulating hormone (TSH) was measured. Thyroid hyperplasia occurred in both groups beginning at 3 months; the thyroid size was greater in the PVPV-Akt1WT mice (
P
<0.001). In comparison with PVPV-Akt1WT mice, thyroid cancer development was delayed in the PVPV-Akt1KO mice (
P
=0.003) and the degree of tumor invasiveness was reduced. The PVPV-Akt1WT mice displayed pulmonary metastases at 12 and 15 months of age, by contrast PVPV-Akt1KO mice did not develop distant metastases at 15 months of age. Despite continued expression of Akt2 or Akt3, pAkt levels were decreased and there was evidence of reduced Akt effect on p27 in the PVPV-Akt1KO thyroids. TSH levels were similarly elevated in PV mice regardless of Akt1 expression. In conclusion, thyroid cancer development and progression in TR β
PV/PV
mice are Akt1-dependent, consistent with a tumor progression-promoting role in this murine thyroid cancer model.</description><subject>631/67/322</subject><subject>692/699/67/1459/1843</subject><subject>Adenoma - blood supply</subject><subject>Adenoma - enzymology</subject><subject>Age</subject><subject>AKT protein</subject><subject>AKT1 protein</subject><subject>AKT2 protein</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Autopsy</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>Carcinoma - blood supply</subject><subject>Carcinoma - enzymology</subject><subject>Carcinoma - secondary</subject><subject>Cell Biology</subject><subject>Cell physiology</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cellular biology</subject><subject>Development and progression</subject><subject>Endocrinopathies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Knock-In Techniques</subject><subject>Hormone receptors</subject><subject>Hormones</subject><subject>Human Genetics</subject><subject>Hyperplasia</subject><subject>Internal Medicine</subject><subject>Invasiveness</subject><subject>Kinases</subject><subject>Lung</subject><subject>Lung Neoplasms - secondary</subject><subject>Malignant tumors</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Miscellaneous</subject><subject>Molecular and cellular biology</subject><subject>Necropsy</subject><subject>Neovascularization, Pathologic - enzymology</subject><subject>Oncology</subject><subject>original-article</subject><subject>Physiological aspects</subject><subject>Protein kinases</subject><subject>Proto-Oncogene Proteins c-akt - deficiency</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Rodents</subject><subject>Thyroid cancer</subject><subject>Thyroid hormone receptors</subject><subject>Thyroid Neoplasms - blood supply</subject><subject>Thyroid Neoplasms - enzymology</subject><subject>Thyroid Neoplasms - pathology</subject><subject>Thyroid-stimulating hormone</subject><subject>Thyroid. Thyroid axis (diseases)</subject><subject>Thyrotropin - blood</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kstv1DAQxiMEotvCjTOyQBUcmsXvxMdVxUuqxAXOltePxSWxi52A9r9nwi5UoIJ88Gj88zczmq9pnhC8Jpj1r3Kya4oJWRMm7zUrwjvZCqH4_WaFlcCtooyeNKe1XmOMO4Xpw-aEEsGoJHLVfN98mQhyPkQbfbJ7CAezr2iax1zQTcm74muNOV2gb6baeTAFxQThz5RJDrlYJ5MmNPrJQFRjBQAZNM4lJo_GDIooBzR93pccHbImWV8eNQ-CGap_fLzPmk9vXn-8fNdefXj7_nJz1VohyNQaBT0TGkwnlHfObYknVgWKfeBCGacoZZIJJygh3bYPvafSWrnlxlsSMGNnzYuDLozydfZ10mOs1g-DST7PVYO-pFIICeTL_5IE475nXLBF9Nlf6HWeS4I5dK8UJbTnHKDn_4Ko5IRjdpA6UjszeB1TyFMxdqmsN7QjYtHqgVrfQcFxfow2J1gf5P_4cHH4YEuutfigb0ocTdnDGHqxjQbb6MU2GmwD-NNjr_N29O43_MsnAJwfATCBGUKBJcZ6y_GO9lItddsDV-Ep7Xy5HfrOwj8Aee_XQg</recordid><startdate>20111020</startdate><enddate>20111020</enddate><creator>Saji, M</creator><creator>Narahara, K</creator><creator>McCarty, S K</creator><creator>Vasko, V V</creator><creator>La Perle, K M</creator><creator>Porter, K</creator><creator>Jarjoura, D</creator><creator>Lu, C</creator><creator>Cheng, S-Y</creator><creator>Ringel, M D</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20111020</creationdate><title>Akt1 deficiency delays tumor progression, vascular invasion, and distant metastasis in a murine model of thyroid cancer</title><author>Saji, M ; Narahara, K ; McCarty, S K ; Vasko, V V ; La Perle, K M ; Porter, K ; Jarjoura, D ; Lu, C ; Cheng, S-Y ; Ringel, M D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551t-a900712fa759edddb1e1c9f20ef459ad9223635d52117b8f8e26cc6b4aec1f033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>631/67/322</topic><topic>692/699/67/1459/1843</topic><topic>Adenoma - blood supply</topic><topic>Adenoma - enzymology</topic><topic>Age</topic><topic>AKT protein</topic><topic>AKT1 protein</topic><topic>AKT2 protein</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Autopsy</topic><topic>Biological and medical sciences</topic><topic>Breast cancer</topic><topic>Carcinoma - blood supply</topic><topic>Carcinoma - enzymology</topic><topic>Carcinoma - secondary</topic><topic>Cell Biology</topic><topic>Cell physiology</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cellular biology</topic><topic>Development and progression</topic><topic>Endocrinopathies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene Knock-In Techniques</topic><topic>Hormone receptors</topic><topic>Hormones</topic><topic>Human Genetics</topic><topic>Hyperplasia</topic><topic>Internal Medicine</topic><topic>Invasiveness</topic><topic>Kinases</topic><topic>Lung</topic><topic>Lung Neoplasms - secondary</topic><topic>Malignant tumors</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Miscellaneous</topic><topic>Molecular and cellular biology</topic><topic>Necropsy</topic><topic>Neovascularization, Pathologic - enzymology</topic><topic>Oncology</topic><topic>original-article</topic><topic>Physiological aspects</topic><topic>Protein kinases</topic><topic>Proto-Oncogene Proteins c-akt - deficiency</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Rodents</topic><topic>Thyroid cancer</topic><topic>Thyroid hormone receptors</topic><topic>Thyroid Neoplasms - blood supply</topic><topic>Thyroid Neoplasms - enzymology</topic><topic>Thyroid Neoplasms - pathology</topic><topic>Thyroid-stimulating hormone</topic><topic>Thyroid. Thyroid axis (diseases)</topic><topic>Thyrotropin - blood</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saji, M</creatorcontrib><creatorcontrib>Narahara, K</creatorcontrib><creatorcontrib>McCarty, S K</creatorcontrib><creatorcontrib>Vasko, V V</creatorcontrib><creatorcontrib>La Perle, K M</creatorcontrib><creatorcontrib>Porter, K</creatorcontrib><creatorcontrib>Jarjoura, D</creatorcontrib><creatorcontrib>Lu, C</creatorcontrib><creatorcontrib>Cheng, S-Y</creatorcontrib><creatorcontrib>Ringel, M D</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>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saji, M</au><au>Narahara, K</au><au>McCarty, S K</au><au>Vasko, V V</au><au>La Perle, K M</au><au>Porter, K</au><au>Jarjoura, D</au><au>Lu, C</au><au>Cheng, S-Y</au><au>Ringel, M D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Akt1 deficiency delays tumor progression, vascular invasion, and distant metastasis in a murine model of thyroid cancer</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2011-10-20</date><risdate>2011</risdate><volume>30</volume><issue>42</issue><spage>4307</spage><epage>4315</epage><pages>4307-4315</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Akt activation is common in progressive thyroid cancer. In breast cancer, Akt1 induces primary cancer growth, but is reported to inhibit metastasis
in vivo
in several model systems. In contrast, clinical and
in vitro
studies suggest a metastasis-promoting role for Akt1 in thyroid cancer. The goal of this study was to determine the functional role of Akt1 in thyroid cancer growth and metastatic progression
in vivo
using thyroid hormone receptor (TR) β
PV/PV
knock-in (PV) mice, which develop metastatic thyroid cancer. We crossed Akt1
−/−
and PV mice and compared tumor development, local progression, metastasis and histology in
TRβ
PV/PV
/Akt1
+/+
(PVPV-Akt1WT) and
TRβ
PV/PV
/Akt1
−/−
(PVPV-Akt1KO) mice. Mice were killed at 3, 6, 9, 12 and 15 months; necropsy was performed and serum thyroid stimulating hormone (TSH) was measured. Thyroid hyperplasia occurred in both groups beginning at 3 months; the thyroid size was greater in the PVPV-Akt1WT mice (
P
<0.001). In comparison with PVPV-Akt1WT mice, thyroid cancer development was delayed in the PVPV-Akt1KO mice (
P
=0.003) and the degree of tumor invasiveness was reduced. The PVPV-Akt1WT mice displayed pulmonary metastases at 12 and 15 months of age, by contrast PVPV-Akt1KO mice did not develop distant metastases at 15 months of age. Despite continued expression of Akt2 or Akt3, pAkt levels were decreased and there was evidence of reduced Akt effect on p27 in the PVPV-Akt1KO thyroids. TSH levels were similarly elevated in PV mice regardless of Akt1 expression. In conclusion, thyroid cancer development and progression in TR β
PV/PV
mice are Akt1-dependent, consistent with a tumor progression-promoting role in this murine thyroid cancer model.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>21532616</pmid><doi>10.1038/onc.2011.136</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0950-9232 1476-5594 |
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| recordid | cdi_proquest_miscellaneous_900626556 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | 631/67/322 692/699/67/1459/1843 Adenoma - blood supply Adenoma - enzymology Age AKT protein AKT1 protein AKT2 protein Animal models Animals Apoptosis Autopsy Biological and medical sciences Breast cancer Carcinoma - blood supply Carcinoma - enzymology Carcinoma - secondary Cell Biology Cell physiology Cell receptors Cell structures and functions Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cellular biology Development and progression Endocrinopathies Fundamental and applied biological sciences. Psychology Gene expression Gene Knock-In Techniques Hormone receptors Hormones Human Genetics Hyperplasia Internal Medicine Invasiveness Kinases Lung Lung Neoplasms - secondary Malignant tumors Medical sciences Medicine Medicine & Public Health Metastases Metastasis Mice Mice, Inbred C57BL Miscellaneous Molecular and cellular biology Necropsy Neovascularization, Pathologic - enzymology Oncology original-article Physiological aspects Protein kinases Proto-Oncogene Proteins c-akt - deficiency Proto-Oncogene Proteins c-akt - metabolism Rodents Thyroid cancer Thyroid hormone receptors Thyroid Neoplasms - blood supply Thyroid Neoplasms - enzymology Thyroid Neoplasms - pathology Thyroid-stimulating hormone Thyroid. Thyroid axis (diseases) Thyrotropin - blood Tumors |
| title | Akt1 deficiency delays tumor progression, vascular invasion, and distant metastasis in a murine model of thyroid cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T14%3A06%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Akt1%20deficiency%20delays%20tumor%20progression,%20vascular%20invasion,%20and%20distant%20metastasis%20in%20a%20murine%20model%20of%20thyroid%20cancer&rft.jtitle=Oncogene&rft.au=Saji,%20M&rft.date=2011-10-20&rft.volume=30&rft.issue=42&rft.spage=4307&rft.epage=4315&rft.pages=4307-4315&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/onc.2011.136&rft_dat=%3Cgale_proqu%3EA271512848%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2641403533&rft_id=info:pmid/21532616&rft_galeid=A271512848&rfr_iscdi=true |