Activation of phosphatidylinositol 3-kinase (PI3K) as a predictor of clinical outcome in breast cancer patients

R. F. Swaby, A. A. Sahin, R. Broaddus, Y. Lu, A. Eder, A. Thornton, G. B. Mills

    Research output: Contribution to journalArticle

    Abstract

    Phosphorylation of membrane phosphatidylinositols by phosphatidylinositol 3-kinase (PI3K) plays a pivotal role in the control of cell proliferation, differentiation, senescence, cytoskeletal organization, motility, metastases, invasion, angiogenesis, and cell survival. This suggests that PI3K may play a critical role in cell growth regulation and potentially tumorigenesis. PI3K phosphorylates membrane phosphatidylinositol bisphosphate-4,5 (PtdIns-4,5) creating phosphatidylinositol-3,4,5 (PtdIns-3,4,5). 3-phosphorylated PtdIns recruit AKT to the cell membrane where it is then phosphorylated by PDK1 and PDK2 to its activated form. Several lines of evidence suggest that activation of AKT is involved in breast cancer development. These include DNA and RNA amplification of AKT in breast cancer tissue samples. Additionally, PTEN/MMAC1, which functions as a tumor suppressor by dephosphorylating PtdIns-3,4,5 thereby rendering it unable to activate AKT, has been found to be mutated in breast cancer, both sporadic and associated with Cowden's Syndrome. We assessed whether PI3K activation and PTEN loss of activity are correlated with clinical outcome in patients with breast cancer. It has previously been difficult to measure cellular PI3K activity from cultured cells and biopsies. We have developed an immunohistochemical technique to stain for the presence of PtdIns-3,4,5, demonstrating PI3K activation in the breast cancer cell line MDA-MB468, and are retrospectively testing archived tissue samples from breast cancer patients. We report the presence of PI3K activation, and its' downstream effector, AKT, with respect to patient outcome.

    Original languageEnglish (US)
    Number of pages1
    JournalBreast Cancer Research and Treatment
    Volume69
    Issue number3
    StatePublished - Jan 1 2001

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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