Induction of Mammary Cancer by Activated Akt
Annual rept. 1 Jul 1999-30 Jun 2000
COLORADO UNIV HEALTH SCIENCES CENTER DENVER
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Breast cancer can be a result of both uncontrolled cellular proliferation and a failure of cells to undergo apoptosis, a genetically controlled process by which cells regulate their own survival. Apoptosis in the mammary gland has been well documented during both virgin development and involution. Numerous studies have shown that the serinethreonine protein kinase Akt can suppress apoptosis. Akt is activated by numerous growth factors, including prolactin, which are involved in mammary development and function. One goal of this proposal is to determine the signaling pathways involved in prolactin-induced Akt activation. Results indicate that prolactin-induced Akt activation is mediated through both the P13-kinase and src-like kinase pathways. In addition, the downstream effects of Akt activation will also be examined. Adenoviruses expressing different Akt constructs have been made and will be used to address this issue. The main goal of this proposal is to determine the role of Akt in the development of mammary cancer. Transgenic mice expressing a constitutively active form of Akt were produced that show a delay in involution caused by suppression of apoptosis of the secretory epithelial cells. We predict that this suppression of apoptosis will result in the development of lesions that may lead to tumors.
- Anatomy and Physiology
- Medicine and Medical Research