The Role of the Phosphadityl Inositol 3' Kinase Coupled Signaling Pathways in Mammary Tumorigenesis
Abstract
The Akt/PKB serine/threonine kinase plays roles in coupling growth factor receptors to cell survival pathways. Although evidence suggests roles for phosphatidylinositol 3'-OH Kinase (PI3K) and Akt in normal mammary development 1 and tumorigenesis, the role of these signaling molecules in these processes remains to be elucidated. To directly assess the role of Akt in mammary epithelial development and tumorigenesis, we have generated transgenic mice that express a constitutively active Akt (Akt-DD) in the mammary epithelium. Although expression of Akt-DD interferes with normal mammary gland involution, mammary tumors were not observed in these strains. To explore the potential role of Akt in mammary tumor progression, mice co-expressing Akt-DD and a mutant form of Polyomavirus middle T (PyV mT) antigen de-coupled from PI3K/Akt signaling pathways were generated. Co-expression of Akt-DD with mutant PyV mT resulted in dramatic acceleration of mammary tumorigenesis. This acceleration was further correlated with reduced apoptotic cell death in mammary epithelium expressing the mutant form of PyV mT. Taken together these observations indicate that activation of Akt can contribute to tumor progression by providing an important cell survival signal.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA398289
Entities
People
- William Muller
Organizations
- McMaster University