Foxp3-RFP+AKT3-/- transgenic mouse strain to study the role of AKT3 in stem cells and tumorigenicity
Breast cancer is one of the cancer types that affect the health of women in many countries and the second leading cause of cancer-related death, behind lung-cancer.
Epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. Axl is a member of the TAM (Tyro-Axl-Mer) receptor tyrosine kinases (RTK) transmembrane receptor tyrosine kinase and have been shown to play a role in EMT in both cancer and development. Furthermore we identified Akt3 as a key downstream effector of Axl in the maintenance of EMT, and stem cell-like activity (Tiron et al., submitted).
The project will consist to breed Foxp3-RFP+AKT3-/- transgenic mouse strain with the lack of expression of the AKT3 protein in a C57bl6/J background.
This strain will allow us to assess the role of AKT3 in EMT in physiological development as well as in tumor development.
The project will only consist in breeding and acute experiment therefore only minimal pain is expected, furthermore animals with evidence of distress will be euthanized.
AKT3 null animals have been obtained in C57Bl6/J background so C57bl6/J mice will be used as control mice. The colony will be started with 2 breeding pairs and will be expended. Compared to our previous breeding projects (fots project 6632, 6638 where we planned to use respectively 1500 and 1000 mice) we plan to use no more than 500 animals. We reduce the number of animals because AKT3 null mice will be breed together and no unwanted genotypes will be obtained.
In order to confirm the role of AKT3 in EMT in both physiological development and during cancer the transgenic mice by comparison with normal mice of the same background will allow seeing and assessing the role of akt3 in a whole organism which is impossible is simpler models like cell culturing.
Epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. Axl is a member of the TAM (Tyro-Axl-Mer) receptor tyrosine kinases (RTK) transmembrane receptor tyrosine kinase and have been shown to play a role in EMT in both cancer and development. Furthermore we identified Akt3 as a key downstream effector of Axl in the maintenance of EMT, and stem cell-like activity (Tiron et al., submitted).
The project will consist to breed Foxp3-RFP+AKT3-/- transgenic mouse strain with the lack of expression of the AKT3 protein in a C57bl6/J background.
This strain will allow us to assess the role of AKT3 in EMT in physiological development as well as in tumor development.
The project will only consist in breeding and acute experiment therefore only minimal pain is expected, furthermore animals with evidence of distress will be euthanized.
AKT3 null animals have been obtained in C57Bl6/J background so C57bl6/J mice will be used as control mice. The colony will be started with 2 breeding pairs and will be expended. Compared to our previous breeding projects (fots project 6632, 6638 where we planned to use respectively 1500 and 1000 mice) we plan to use no more than 500 animals. We reduce the number of animals because AKT3 null mice will be breed together and no unwanted genotypes will be obtained.
In order to confirm the role of AKT3 in EMT in both physiological development and during cancer the transgenic mice by comparison with normal mice of the same background will allow seeing and assessing the role of akt3 in a whole organism which is impossible is simpler models like cell culturing.