Functional Analysis of Oncogene Akt: Its Role in Tumorigenesis in Vivo and Cell Cycle Progression in Vitvo

摘要

Breast cancer is the most common malignancy in women. The recently identified tumor suppressor gene PTEN has turned out to be a promising candidate for mammary tumorigenesis. Mice heterozygous for PTEN develops mammary tumors starting from 6 weeks. The goal of this project is to determine the role of AKT, a major downstream target of PI3K pathway, in PTEN mediated mammary tumor development. To study the function of AKT in breast cancer development, we have deleted AKT gene and are studying its role both in vivo and in vitro. In cell culture, we demonstrated that AKT is not only responsible for the survival phenotype but also important for the cell proliferation phenotype of PTEN null ES cells. In vivo analysis demonstrated that deletion of AKT on top of PTEN resulted in both decreased tumor occurrence and shorter tumor onset.