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Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse.
Conway, James R W; Warren, Sean C; Lee, Young-Kyung; McCulloch, Andrew T; Magenau, Astrid; Lee, Victoria; Metcalf, Xanthe L; Stoehr, Janett; Haigh, Katharina; Abdulkhalek, Lea; Guaman, Cristian S; Reed, Daniel A; Murphy, Kendelle J; Pereira, Brooke A; Mélénec, Pauline; Chambers, Cecilia; Latham, Sharissa L; Lenthall, Helen; Deenick, Elissa K; Ma, Yuanqing; Phan, Tri; Lim, Elgene; Joshua, Anthony M; Walters, Stacey; Grey, Shane T; Shi, Yan-Chuan; Zhang, Lei; Herzog, Herbert; Croucher, David R; Philp, Andy; Scheele, Colinda L G J; Herrmann, David; Sansom, Owen J; Morton, Jennifer P; Papa, Antonella; Haigh, Jody J; Nobis, Max; Timpson, Paul.
Afiliación
  • Conway JRW; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Warren SC; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Lee YK; Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
  • McCulloch AT; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Magenau A; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Lee V; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Metcalf XL; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Stoehr J; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Haigh K; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Abdulkhalek L; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Guaman CS; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Reed DA; School of Clinical Medicine, UNSW Sydney, Randwick Clinical Campus, Sydney, NSW, Australia.
  • Murphy KJ; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Pereira BA; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Mélénec P; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Chambers C; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Latham SL; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Lenthall H; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Deenick EK; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Ma Y; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Phan T; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Lim E; Department of Pharmacology and Therapeutics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Joshua AM; CancerCare Manitoba Research Institute, Winnipeg, Manitoba, Canada.
  • Walters S; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Grey ST; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Shi YC; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Zhang L; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Herzog H; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Croucher DR; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Philp A; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Scheele CLGJ; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Herrmann D; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Sansom OJ; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Morton JP; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Papa A; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Haigh JJ; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
  • Nobis M; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
  • Timpson P; Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW 2010, Australia.
Sci Adv ; 9(17): eadf9063, 2023 04 28.
Article en En | MEDLINE | ID: mdl-37126544
ABSTRACT
Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT activation can be monitored in real time in diverse tissues, including in individual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Técnicas Biosensibles / Proteínas Proto-Oncogénicas c-akt Límite: Animals Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Australia
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Técnicas Biosensibles / Proteínas Proto-Oncogénicas c-akt Límite: Animals Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Australia