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The PTEN/PI3K/AKT Pathway in vivo, Cancer Mouse Models
Amancio Carnero1, Jesus M Paramio2
1Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla , Seville , Spain.
Abstract:
When PI3K (phosphatidylinositol-3 kinase) is activated by receptor tyrosine kinases, it phosphorylates PIP2 to generate PIP3 and activates the signaling pathway. Phosphatase and tensin homolog deleted on chromosome 10 dephosphorylates PIP3 to PIP2, and thus, negatively regulates the pathway. AKT (v-akt murine thymoma viral oncogene homolog; protein kinase B) is activated downstream of PIP3 and mediates physiological processes. Furthermore, substantial crosstalk exists with other signaling networks at all levels of the PI3K pathway. Because of its diverse array, gene mutations, and amplifications and also as a consequence of its central role in several signal transduction pathways, the PI3K-dependent axis is frequently activated in many tumors and is an attractive therapeutic target. The preclinical testing and analysis of these novel therapies requires appropriate and well-tailored systems. Mouse models in which this pathway has been genetically modified have been essential in understanding the role that this pathway plays in the tumorigenesis process. Here, we review cancer mouse models in which the PI3K/AKT pathway has been genetically modified.
Insights
The phosphatidylinositol-3 kinase (PI3K)/AKT pathway is crucial in cancer development and a key therapeutic target. This review examines genetically modified mouse models essential for studying PI3K/AKT pathway roles in tumorigenesis and preclinical therapy testing.
Area of Science:
- Oncology
- Molecular Biology
- Signaling Pathways
Background:
- The PI3K/AKT pathway regulates cell growth and survival.
- Dysregulation of this pathway, via mutations or amplifications, is common in various cancers.
- This pathway's central role and crosstalk with other networks make it a significant therapeutic target.
Purpose of the Study:
- To review genetically modified mouse models of the PI3K/AKT pathway.
- To highlight the importance of these models in understanding tumorigenesis.
- To discuss their utility in preclinical testing of novel cancer therapies.
Main Methods:
- Review of existing literature on PI3K/AKT pathway mouse models.
- Analysis of genetic modifications within these models.
- Evaluation of their application in cancer research.
Main Results:
- Genetically modified mouse models are indispensable tools for dissecting the PI3K/AKT pathway's function in cancer.
- These models recapitulate key aspects of human tumorigenesis driven by PI3K/AKT.
- They facilitate the evaluation of targeted therapies.
Conclusions:
- Mouse models with genetic alterations in the PI3K/AKT pathway are vital for cancer research.
- They provide critical insights into pathway-driven tumorigenesis.
- These models are essential for advancing the development of effective cancer treatments targeting this axis.
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