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Published on: June 7, 2019
Mouse models of PIK3CA mutations: one mutation initiates heterogeneous mammary tumors
Shany Koren1, Mohamed Bentires-Alj
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Abstract:
The phosphoinositide 3-kinase (PI3K) signaling pathway is crucial for cell growth, proliferation, metabolism, and survival, and is frequently deregulated in human cancer, including ~ 70% of breast tumors. PIK3CA, the gene encoding the catalytic subunit p110α of PI3K, is mutated in ~ 30% of breast cancers. However, the exact mechanism of PIK3CA-evoked breast tumorigenesis has not yet been defined. Genetically engineered mouse models are valuable for examining the initiation, development and progression of cancer. Transgenic mice harboring hotspot mutations in p110α have helped to elucidate breast cancer pathogenesis and increase our knowledge about molecular and cellular alterations in vivo. They are also useful for the development of therapeutic strategies. Here, we describe current mouse models of mutant PIK3CA in the mammary gland, and discuss differences in tumor latency and pathogenesis.
Insights
Mutant PIK3CA drives breast cancer by altering cell growth and survival. Mouse models reveal how these PI3K pathway changes initiate and progress tumors, aiding therapeutic development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The phosphoinositide 3-kinase (PI3K) pathway regulates essential cellular functions and is often dysregulated in cancers.
- Mutations in PIK3CA, encoding the p110α subunit of PI3K, are found in approximately 30% of breast cancers.
- The precise mechanisms of PIK3CA-driven breast tumorigenesis remain incompletely understood.
Purpose of the Study:
- To review current genetically engineered mouse models of mutant PIK3CA in mammary gland development.
- To discuss how these models illuminate PIK3CA-evoked breast cancer initiation, progression, and pathogenesis.
- To highlight the utility of these models for evaluating therapeutic strategies.
Main Methods:
- Utilizing transgenic mouse models harboring hotspot mutations in the PIK3CA gene within the mammary gland.
- Analyzing tumor latency, pathogenesis, and molecular/cellular alterations in vivo.
- Comparing different mouse models to understand variations in disease development.
Main Results:
- Genetically engineered mouse models with PIK3CA mutations provide insights into breast cancer pathogenesis.
- These models demonstrate the role of PIK3CA mutations in initiating and driving tumor development.
- Variations in tumor latency and specific pathogenic features are observed across different models.
Conclusions:
- Mouse models of mutant PIK3CA are instrumental in dissecting breast cancer development.
- Understanding in vivo alterations is key to defining PIK3CA's role in tumorigenesis.
- These models are crucial for advancing the development of targeted breast cancer therapies.
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